BI-78D3 functions as a substrate competitive inhibitor of JNK, inhibit the JNK kinase activity (IC50=280 nM).
IC50 & Target[1]
JNK
280 nM (IC50)
体外研究 (In Vitro)
BI-78D3, dose-dependently inhibits the phosphorylation of JNK substrates both in vitro and in cell. BI-78D3 is able to compete with the D-domain of JIP1 (amino acids 153-163; pepJIP1) for JNK1 binding (IC50=500 nM). Using the same in vitro LanthaScreen kinase assay and the same ATF2 substrate, BI-78D3 is found to be 100-fold less active vs. p38α, a member of the MAPK family with high structural similarity to JNK, and completely inactive against mTOR and PI3-kinase (α-isoform), both unrelated protein kinases. Furthermore, Lineweaver-Burk analysis clearly indicates that BI-78D3 is competitive with ATF2 for binding to JNK1 with an apparent Ki value of 200 nM. In an attempt to profile the properties of BI-78D3 in the context of a complex cellular milieu, the cell-based LanthaScreen kinase assay is used. In this assay BI-78D3 is able to inhibit TNF-α stimulated phosphorylation of c-Jun in cell (EC50=12.4 μM)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
The link between ConA-induced liver failure, TNF receptor signaling, and JNK function has been established by studies employing JNK1-/- and JNK2-/- mice. For this analysis, insulin insensitive mice are injected only once with 25 mg/kg BI-78D3, 30 min before insulin injection. The effect of insulin on blood glucose levels is then measured. BI-78D3 results in a statistically significant reduction in blood glucose levels as compared with the vehicle control. Thus, the ability of BI-78D3 to abrogate ConA-induced liver damage and restore insulin sensitivity is consistent with its proposed function as an effective JNK inhibitor. Liquid chromatography/mass spectrometry bio-availability analysis demonstrates that BI-78D3 has favorable microsome and plasma stability (T1/2=54 min)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
379.37
Formula
C13H9N5O5S2
CAS 号
883065-90-5
运输条件
Room temperature in continental US; may vary elsewhere.
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. Stebbins JL et al. Identification of a new JNK inhibitor targeting the JNK-JIP interaction site. Proc Natl Acad Sci U S A, 2008 Oct 28, 105(43):16809-13.
Kinase Assay [1]
The cell based kinase assays for c-Jun and ATF2 phosphorylation carry out by using the LanthaScreen c-Jun (1-79) HeLa and LanthaScreen ATF2 (19-106) A549 cell lines which stably express GFP-c-Jun 1-79 and GFP-ATF2 19-106, respectively. Phosphorylation is determined by measuring the time resolved FRET (TR-FRET) between a terbium labeled phospho-specific antibody and the GFP-fusion protein. The cells are plated in white tissue culture treated 384 well plates at a density of 10,000 cell per well in 32 μl assay medium (supplemented with 1% charcoal/dextran-treated FBS, 100 U/mL Penicillin and 100 μg/mL Streptomycin, 0.1 mM nonessential amino acids, 1 mM sodium pyruvate, 25 mM Hepes, pH 7.3, and lacking phenol red). After overnight incubation, cells are pretreated for 60 min with BI-78D3 (0.001, 0.01, 0.1, 1, 10, and 100 μM) followed by 30 min of stimulation with 2 ng/mL of TNF-α that stimulates both JNK and p38. The medium is then removed by aspiration and the cells are lysed by adding 20 μL of lysis buffer (20 mM Tris•HCl, pH 7.6, 5 mM EDTA, 1% Nonidet P-40 substitute, 5 mM NaF, 150 mM NaCl, and 1:100 protease and phosphatase inhibitor mix, SIGMA P8340 and P2850, respectively). The lysis buffer includs 2 nM of the terbium-labeled anti-pc-Jun (pSer73) or anti-pATF2 (pThr71) detection antibodies. After allowing the assay to equilibrate for 1 h at room temperature, TR-FRET emission ratios are determined on a BMG Pherastar fluorescence plate reader (excitation at 340 nm, emission 520 nm and 490 nm; 100 μs lag time, 200 μs integration time, emission ratio=Em520/Em 490)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
Mice[1] ConA and BI-78D3 is injected i.v. at 10 mg/kg into 6 to 8 weeks old male BL/6 mice. For partial hepatectomy, mice are anesthetized with isofluorane and subjected to midventral laparotomy followed by removal of the left lateral and median lobes. Animals are killed, blood is collected by cardiac puncture, and livers are surgically removed. Serum is separated and analyzed for alanine-aminotranferase levels[1]. Eleven-week-old male BKS.Cg-+Leprdb/+Leprdb/OlaHsd db/db mice are randomized based on blood glucose levels acclimated three days before drug dosing. Blood glucose is read by using a hand-held glucose meter (Mice are fasted 6 h before i.p. (i.p.) administration of 25 mg/kg BI-78D3. Thirty minutes after test article administration, Bovine Insulin (I-0516 at 0.75 mg/kg) is administered via i.p. injection. Blood samples are taken at designated time points and blood glucose levels are measured as described. Food is returned three hours after test article administration[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Stebbins JL et al. Identification of a new JNK inhibitor targeting the JNK-JIP interaction site. Proc Natl Acad Sci U S A, 2008 Oct 28, 105(43):16809-13.
BI8626 is a specific inhibitor of the ubiquitin ligase HUWE1 with an IC50 of 0.9 μM[1].
IC50 & Target
IC50: 0.9 μM (HUWE1)[1]
体外研究 (In Vitro)
BI8626 induces HUWE1 ectopically expresses to abolishe ubiquitination of MCL1 in HeLa cells[1]. BI8626 suppresses colony formation of Ls174T cells with estimated IC50 value of 0.7 μM, and BI8622 (1-4 days) treatment retards passage of Ls174T cells through all phases of the cell cycle, with the effect being strongest for G1[1]. BI8626 (0-50 μM; 0-6 hours) retards the degradation of MCL1 in response to UV irradiation to the same extent as depletion of HUWE1 in U2OS cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cycle Analysis[1]
Cell Line:
Ls174T cells
Concentration:
0 μM, 5 μM,10 μM, 15 μM, 20 μM
Incubation Time:
0-4 days
Result:
Retarded passage of Ls174T cells through all phases of the cell cycle, with the effect being strongest for G1.
Western Blot Analysis[1]
Cell Line:
U2OS cells
Concentration:
0 μM, 20 μM, 50 μM
Incubation Time:
0 hour,1 hour,2 hours,4 hours,6 hours
Result:
Retarded the degradation of MCL1 in response to UV irradiation in HeLa cells by inhibiting HUWE1 in U2OS cells.
分子量
440.54
Formula
C25H28N8
CAS 号
1875036-75-1
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Peter S, et al. Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase.EMBO Mol Med. 2014 Dec;6(12):1525-41.
BI-7273 is a selective, and cell-permeable BRD9 inhibitor, with an IC50 and a Kd of 19 and 0.75 nM; also shows high effect on BRD7, with an IC50 and a Kd of 117 nM and 0.3 nM.
BI-7273 is a selective, and cell-permeable BRD9 inhibitor, with an IC50 and a Kd of 19 and 0.75 nM; also shows high effect on BRD7, with an IC50 and a Kd of 117 nM and 0.3 nM. BI-7273 also has slight activity against a panel of kinases such as CECR2, BRPF1, BRD1, CREBBP, EP300, FALZ, TAF1(2) and TAF1L(2), with Kds of 8.8 nM, 210 nM, 2600 nM, 8600 nM, 10000 nM, 850 nM, 1000 nM, and 1200 nM, respectively. BI-7273 (1 μM) is active in U2OS cell lines. BI-7273 blocks EOL-1 cell proliferation with EC50 of 1400 nM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
353.41
Formula
C20H23N3O3
CAS 号
1883429-21-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Martin LJ, et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75.
Kinase Assay [1]
His-tagged BRD9 is immobilized to a density of 2000-4000 RUs on flow cells 3 and 4 of a Biacore NTA-chip. Carbonic anhydrase II is immobilized at a similar density on flow cell 2 and a blank reference surface is generated on flow cell 1. The buffer is then switched to assay buffer (HBS-P+ = 10 mM HEPES, pH 7.4, 150 mM NaCl, 0.05 % P20 + 5 % DMSO) and the chip equilibrated for several hours before use for Kd determinations. To be able to correct for differences in bulk solvent refractive index caused by small variations in the DMSO concentration solvent correction samples are included at the beginning and end of the run. Compounds (BI-7273, etc.) are injected in concentration series (1:1 dilutions, 7 different concentrations), starting with a maximum concentration that is approximately 10-20-fold higher than the expected Kd. The concentration series are prepared in 96-well plates. In the case that the dilution window chosen for a particular compound does not appropriately bracket the Kd of the compound the measurement is repeated with an optimized starting concentration. Positive and negative control samples are included at regular intervals to be able to monitor the performance of the assay. CBS is used as a positive control for carbonic anhydrase II to check for integrity of the reference protein at regular intervals. To correct for the excluded volume effect a DMSO calibration series is prepared and the calibration samples are measured at the beginning and end of each run. Kd values are determined and averaged[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
Cells are grown in 50 µL medium for 7 days starting with 500 and with 1000 cells per well of a 384 well plate in the presence of varying concentrations of compound (BI-7273, etc.) before measuring viability via cellular ATP levels using the cell titer glow assay[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Martin LJ, et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75.
BI-7273 is a selective, and cell-permeable BRD9 inhibitor, with an IC50 and a Kd of 19 and 0.75 nM; also shows high effect on BRD7, with an IC50 and a Kd of 117 nM and 0.3 nM.
BI-7273 is a selective, and cell-permeable BRD9 inhibitor, with an IC50 and a Kd of 19 and 0.75 nM; also shows high effect on BRD7, with an IC50 and a Kd of 117 nM and 0.3 nM. BI-7273 also has slight activity against a panel of kinases such as CECR2, BRPF1, BRD1, CREBBP, EP300, FALZ, TAF1(2) and TAF1L(2), with Kds of 8.8 nM, 210 nM, 2600 nM, 8600 nM, 10000 nM, 850 nM, 1000 nM, and 1200 nM, respectively. BI-7273 (1 μM) is active in U2OS cell lines. BI-7273 blocks EOL-1 cell proliferation with EC50 of 1400 nM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
353.41
Formula
C20H23N3O3
CAS 号
1883429-21-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Martin LJ, et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75.
Kinase Assay [1]
His-tagged BRD9 is immobilized to a density of 2000-4000 RUs on flow cells 3 and 4 of a Biacore NTA-chip. Carbonic anhydrase II is immobilized at a similar density on flow cell 2 and a blank reference surface is generated on flow cell 1. The buffer is then switched to assay buffer (HBS-P+ = 10 mM HEPES, pH 7.4, 150 mM NaCl, 0.05 % P20 + 5 % DMSO) and the chip equilibrated for several hours before use for Kd determinations. To be able to correct for differences in bulk solvent refractive index caused by small variations in the DMSO concentration solvent correction samples are included at the beginning and end of the run. Compounds (BI-7273, etc.) are injected in concentration series (1:1 dilutions, 7 different concentrations), starting with a maximum concentration that is approximately 10-20-fold higher than the expected Kd. The concentration series are prepared in 96-well plates. In the case that the dilution window chosen for a particular compound does not appropriately bracket the Kd of the compound the measurement is repeated with an optimized starting concentration. Positive and negative control samples are included at regular intervals to be able to monitor the performance of the assay. CBS is used as a positive control for carbonic anhydrase II to check for integrity of the reference protein at regular intervals. To correct for the excluded volume effect a DMSO calibration series is prepared and the calibration samples are measured at the beginning and end of each run. Kd values are determined and averaged[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
Cells are grown in 50 µL medium for 7 days starting with 500 and with 1000 cells per well of a 384 well plate in the presence of varying concentrations of compound (BI-7273, etc.) before measuring viability via cellular ATP levels using the cell titer glow assay[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Martin LJ, et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75.
Nevirapine is a non-nucleoside inhibitor of HIV-1 reverse transcriptase used to treat and prevent HIV/AIDS; with a Ki of 270 μM[1].
IC50 & Target
Ki: 270 μM (HIV-1 reverse transcriptase)[1]
体外研究 (In Vitro)
Nevirapine itself is an inhibitor of only CYP3A4 at concentrations that are well above those of therapeutic relevance (Ki=270 μM)[1]. Nevirapine has been used as a re-differentiation agent to treat cancers in several human cancer models. At all doses (100, 200, 350, 500 μM) tested, nevirapine significantly inhibits cell proliferation after 48 h treatment. At high dose (500 μM), nevirapine significantly increases the percentage of apoptotic cells compared with control[2]. Nevirapine is a potent and selective inhibitor (IC50=10-100 nM) of the replication of a wide variety of HIV-1 strains in several cellular assays[3].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Nevirapine is available for use in combination with nucleoside HIV-1 reverse transcriptase inhibitors (e.g., zidovudine, didanosine, etc.). Nevirapine has received FDA approval for use in combination with HIV-1 protease inhibitors (e.g., saquinavir, ritonavir, indinavir, etc.). In humans, nevirapine is eliminated primarily in the urine as glucuronide conjugates of 2-, 3-, 8-, and 12-hydroxynevirapine[1]. Nevirapine is completely absorbed in both sexes of mouse, rat, rabbit, monkey, and chimpanzee. Nevirapine is extensively metabolized in both sexes of all animal species studied[4]. Nevirapine (9 mg/kg, 18 mg/kg and 36 mg/kg) shows significant reduction in ulcer severity score and ulcer index as compared to the control[5]
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
266.30
Formula
C15H14N4O
CAS 号
129618-40-2
中文名称
奈韦拉平;萘维拉平;那韦拉平;奈韦那平;萘韦拉平
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Erickson DA, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitornevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999 Dec;27(12):1488-95.
[2]. Dong JJ, et al. In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Mol Cell Endocrinol. 2013 May 6;370(1-2):113-8.
[3]. Merluzzi VJ, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411-3.
[4]. Riska PS, et al. Biotransformation of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, in mice, rats, rabbits, dogs, monkeys, and chimpanzees. Drug Metab Dispos. 1999 Dec;27(12):1434-47.
[5]. Onasanwo SA, et al. Evaluation of anti-ulcerogenic and ulcer-healing activities of nevirapine in rats. Afr J Med Med Sci. 2015 Sep;44(3):251-9.
Cell Assay [2]
FRO cells are seeded into 96-well culture plates at 10,000 cells/well. Cells are treated with different doses of nevirapine (0, 100, 200, 350 and 500 μM) for 48 h. MTT dye (5 mg/mL) is added to each well for additional 4 h, and the reaction is then stopped by the addition of DMSO. Optical density is measured at 490 nm on a multi-well plate reader[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [4]
Rats: Nevirapine and [14C] Nevirapine are dissolved together in absolute ethanol and methylene chloride (1:1, v/v) with mild heating. The concentration of drug in suspension is 2 mg/mL (20 mg/kg, 26 μCi) for oral dosing to rats and 6.7 mg/mL (20.3 mg/kg, 10 μCi males, 8.9 μCi females) for intraduodenal administration to rats before bile collection. The i.v. dose is administered to rats (1.1 mg/kg, 20 μCi) as a solution in 20% ethanol/80% saline[4].
Mice: Nevirapine and [14C] Nevirapine are dissolved together in absolute ethanol and methylene chloride (1:1, v/v) with mild heating. The concentration of drug in suspension is 2 mg/mL (20 mg/kg, 2.5 μCi) with a specific activity of 5.55 μCi/mg for oral dosing to mice[4].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Erickson DA, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitornevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999 Dec;27(12):1488-95.
[2]. Dong JJ, et al. In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Mol Cell Endocrinol. 2013 May 6;370(1-2):113-8.
[3]. Merluzzi VJ, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411-3.
[4]. Riska PS, et al. Biotransformation of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, in mice, rats, rabbits, dogs, monkeys, and chimpanzees. Drug Metab Dispos. 1999 Dec;27(12):1434-47.
[5]. Onasanwo SA, et al. Evaluation of anti-ulcerogenic and ulcer-healing activities of nevirapine in rats. Afr J Med Med Sci. 2015 Sep;44(3):251-9.
Nevirapine is a non-nucleoside inhibitor of HIV-1 reverse transcriptase used to treat and prevent HIV/AIDS; with a Ki of 270 μM[1].
IC50 & Target
Ki: 270 μM (HIV-1 reverse transcriptase)[1]
体外研究 (In Vitro)
Nevirapine itself is an inhibitor of only CYP3A4 at concentrations that are well above those of therapeutic relevance (Ki=270 μM)[1]. Nevirapine has been used as a re-differentiation agent to treat cancers in several human cancer models. At all doses (100, 200, 350, 500 μM) tested, nevirapine significantly inhibits cell proliferation after 48 h treatment. At high dose (500 μM), nevirapine significantly increases the percentage of apoptotic cells compared with control[2]. Nevirapine is a potent and selective inhibitor (IC50=10-100 nM) of the replication of a wide variety of HIV-1 strains in several cellular assays[3].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Nevirapine is available for use in combination with nucleoside HIV-1 reverse transcriptase inhibitors (e.g., zidovudine, didanosine, etc.). Nevirapine has received FDA approval for use in combination with HIV-1 protease inhibitors (e.g., saquinavir, ritonavir, indinavir, etc.). In humans, nevirapine is eliminated primarily in the urine as glucuronide conjugates of 2-, 3-, 8-, and 12-hydroxynevirapine[1]. Nevirapine is completely absorbed in both sexes of mouse, rat, rabbit, monkey, and chimpanzee. Nevirapine is extensively metabolized in both sexes of all animal species studied[4]. Nevirapine (9 mg/kg, 18 mg/kg and 36 mg/kg) shows significant reduction in ulcer severity score and ulcer index as compared to the control[5]
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
266.30
Formula
C15H14N4O
CAS 号
129618-40-2
中文名称
奈韦拉平;萘维拉平;那韦拉平;奈韦那平;萘韦拉平
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Erickson DA, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitornevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999 Dec;27(12):1488-95.
[2]. Dong JJ, et al. In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Mol Cell Endocrinol. 2013 May 6;370(1-2):113-8.
[3]. Merluzzi VJ, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411-3.
[4]. Riska PS, et al. Biotransformation of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, in mice, rats, rabbits, dogs, monkeys, and chimpanzees. Drug Metab Dispos. 1999 Dec;27(12):1434-47.
[5]. Onasanwo SA, et al. Evaluation of anti-ulcerogenic and ulcer-healing activities of nevirapine in rats. Afr J Med Med Sci. 2015 Sep;44(3):251-9.
Cell Assay [2]
FRO cells are seeded into 96-well culture plates at 10,000 cells/well. Cells are treated with different doses of nevirapine (0, 100, 200, 350 and 500 μM) for 48 h. MTT dye (5 mg/mL) is added to each well for additional 4 h, and the reaction is then stopped by the addition of DMSO. Optical density is measured at 490 nm on a multi-well plate reader[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [4]
Rats: Nevirapine and [14C] Nevirapine are dissolved together in absolute ethanol and methylene chloride (1:1, v/v) with mild heating. The concentration of drug in suspension is 2 mg/mL (20 mg/kg, 26 μCi) for oral dosing to rats and 6.7 mg/mL (20.3 mg/kg, 10 μCi males, 8.9 μCi females) for intraduodenal administration to rats before bile collection. The i.v. dose is administered to rats (1.1 mg/kg, 20 μCi) as a solution in 20% ethanol/80% saline[4].
Mice: Nevirapine and [14C] Nevirapine are dissolved together in absolute ethanol and methylene chloride (1:1, v/v) with mild heating. The concentration of drug in suspension is 2 mg/mL (20 mg/kg, 2.5 μCi) with a specific activity of 5.55 μCi/mg for oral dosing to mice[4].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Erickson DA, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitornevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999 Dec;27(12):1488-95.
[2]. Dong JJ, et al. In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Mol Cell Endocrinol. 2013 May 6;370(1-2):113-8.
[3]. Merluzzi VJ, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411-3.
[4]. Riska PS, et al. Biotransformation of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, in mice, rats, rabbits, dogs, monkeys, and chimpanzees. Drug Metab Dispos. 1999 Dec;27(12):1434-47.
[5]. Onasanwo SA, et al. Evaluation of anti-ulcerogenic and ulcer-healing activities of nevirapine in rats. Afr J Med Med Sci. 2015 Sep;44(3):251-9.
BI-6015 is a hepatocyte nuclear factor 4α (HNF4α) antagonist that can inhibit the expression of known HNF4α target genes. BI6015 represses insulin promoter activity through HNF4α antagonism. BI-6015 can be used for the research of cancer and diabetes[1].
IC50 & Target
hepatocyte nuclear factor 4α (HNF4α)[1]
体外研究 (In Vitro)
BI-6015 (1.25-20 μM; 24-72 h) is cytotoxic to human hepatocellular carcinoma (HCC)[1]. BI-6015 (2.5-10 μM; 5-48 h) inhibits HNF4α gene expression in HepG2 cells[1]. BI-6015 (5 μM; 3 d) induces hepatic steatosis in primary murine hepatocytes[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
Hep3B-Luc cells and primary hepatocytes
Concentration:
1.25, 2.5, 5, 10, 20 μM
Incubation Time:
24, 48, 72 hours
Result:
Was markedly toxic to Hep3B cells but spared primary hepatocytes.
体内研究 (In Vivo)
BI-6015 (10-30 mg/kg; i.p. once daily for 5 days) induces loss of HNF4α expression and hepatic steatosis in mice[1]. BI-6015 (10-30 mg/kg; i.p. daily or every other day for 20-57 days) induces apoptosis in a human hepatocellular carcinoma mouse model[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
331.35
Formula
C15H13N3O4S
CAS 号
93987-29-2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Kiselyuk A, et, al. HNF4α antagonists discovered by a high-throughput screen for modulators of the human insulin promoter. Chem Biol. 2012 Jul 27;19(7):806-18.
BI-9321 is a potent, selective and cellular active nuclear receptor-binding SET domain 3 (NSD3)-PWWP1 domain antagonist with a Kd value of 166 nM. BI-9321 is inactive against NSD2-PWWP1 and NSD3-PWWP2. BI-9321 specifically disrupts histone interactions of the NSD3-PWWP1 domain with an IC50 of 1.2 μM in U2OS cells[1].
IC50 & Target
Kd: 166 nM (NSD3-PWWP1)[1]
体外研究 (In Vitro)
BI-9321 is targeting the methyl-lysine binding site of the PWWP1 domain with sub-micromolar in vitro activity and cellular target engagement at 1 µM. As a single agent, BI-9321 downregulates Myc messenger RNA expression and reduces proliferation in MOLM-13 cells[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
360.43
Formula
C22H21FN4
CAS 号
2387510-86-1
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Böttcher J, et al. Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3. Nat Chem Biol. 2019 Aug;15(8):822-829.
BI-9321 is a potent, selective and cellular active nuclear receptor-binding SET domain 3 (NSD3)-PWWP1 domain antagonist with a Kd value of 166 nM. BI-9321 is inactive against NSD2-PWWP1 and NSD3-PWWP2. BI-9321 specifically disrupts histone interactions of the NSD3-PWWP1 domain with an IC50 of 1.2 μM in U2OS cells[1].
IC50 & Target
Kd: 166 nM (NSD3-PWWP1)[1]
体外研究 (In Vitro)
BI-9321 is targeting the methyl-lysine binding site of the PWWP1 domain with sub-micromolar in vitro activity and cellular target engagement at 1 µM. As a single agent, BI-9321 downregulates Myc messenger RNA expression and reduces proliferation in MOLM-13 cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
360.43
Formula
C22H21FN4
CAS 号
2387510-86-1
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Böttcher J, et al. Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3. Nat Chem Biol. 2019 Aug;15(8):822-829.
BI-9321 is a potent, selective and cellular active nuclear receptor-binding SET domain 3 (NSD3)-PWWP1 domain antagonist with a Kd value of 166 nM. BI-9321 is inactive against NSD2-PWWP1 and NSD3-PWWP2. BI-9321 specifically disrupts histone interactions of the NSD3-PWWP1 domain with an IC50 of 1.2 μM in U2OS cells[1].
IC50 & Target
Kd: 166 nM (NSD3-PWWP1)[1]
体外研究 (In Vitro)
BI-9321 is targeting the methyl-lysine binding site of the PWWP1 domain with sub-micromolar in vitro activity and cellular target engagement at 1 µM. As a single agent, BI-9321 downregulates Myc messenger RNA expression and reduces proliferation in MOLM-13 cells[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
360.43
Formula
C22H21FN4
CAS 号
2387510-86-1
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Böttcher J, et al. Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3. Nat Chem Biol. 2019 Aug;15(8):822-829.
BI-9321 trihydrochloride is a potent, selective and cellular active nuclear receptor-binding SET domain 3 (NSD3)-PWWP1 domain antagonist with a Kd value of 166 nM. BI-9321 trihydrochloride is inactive against NSD2-PWWP1 and NSD3-PWWP2. BI-9321 trihydrochloride specifically disrupts histone interactions of the NSD3-PWWP1 domain with an IC50 of 1.2 μM in U2OS cells[1].
IC50 & Target
Kd: 166 nM (NSD3-PWWP1)[1]
体外研究 (In Vitro)
BI-9321 trihydrochloride is targeting the methyl-lysine binding site of the PWWP1 domain with sub-micromolar in vitro activity and cellular target engagement at 1 µM. As a single agent, BI-9321 trihydrochloride downregulates Myc messenger RNA expression and reduces proliferation in MOLM-13 cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
469.81
Formula
C22H24Cl3FN4
CAS 号
2387510-87-2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
4°C, stored under nitrogen, away from moisture
*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)
溶解性数据
In Vitro:
DMSO : 250 mg/mL (532.13 mM; Need ultrasonic)
H2O : 25 mg/mL (53.21 mM; Need ultrasonic)
配制储备液
浓度溶剂体积质量
1 mg
5 mg
10 mg
1 mM
2.1285 mL
10.6426 mL
21.2852 mL
5 mM
0.4257 mL
2.1285 mL
4.2570 mL
10 mM
0.2129 mL
1.0643 mL
2.1285 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:
BI-2852 is a KRAS inhibitor for the switch I/II pocket (SI/II-pocket) by structure-based drug design with nanomolar affinity. BI-2852 is mechanistically distinct from covalent KRASG12C inhibitor (binds to switch II pocket) and binds ten-fold more strongly to active KRASG12D versus KRASwt (740 nM vs 7.5 μM). BI-2852 blocks GEF, GAP, and effector interactions with KRAS, leading to inhibition of downstream signaling and an antiproliferative effect in KRAS mutant cells[1].
IC50 & Target[1]
KRAS(G12C)
450 nM (IC50)
KRAS(G12C)
750 nM (Kd)
体外研究 (In Vitro)
BI-2852 (Compound 1) (10 nM-10 µM; 2 hours) shows a dose-dependent pERK modulation and antiproliferative effect at EC50s of 5.8 µM and 6.7 µM in soft agar and low serum conditions in NCI-H358 cells[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
516.59
Formula
C31H28N6O2
CAS 号
2375482-51-0
运输条件
Room temperature in continental US; may vary elsewhere.
BI-3406 (compound I-6) is an orally active, highly potent and selective inhibitor of the interaction between KRAS and Son of Sevenless 1 (SOS1) with an IC50 of 6 nM. BI-3406 potently reduces the formation of GTP-loaded KRAS, and inhibits MAPK pathway signaling. BI-3406 has anticancer activity[1][2].
IC50 & Target[1]
KRAS-SOS1
6 nM (IC50)
体外研究 (In Vitro)
BI-3406 is an inhibitor of the interaction between KRAS and its Guanine Nucleotide Exchange Factor (GEF) SOS1. BI-3406 does not block the interaction of KRAS with SOS2 but elicits activity on a broad panel of KRAS oncogenic variants, including all major G12 and G13 oncoproteins. Down-modulation of this signaling cascade by BI-3406 in KRAS G12 or G13 mutant cells effectively limits cell proliferation[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
462.46
Formula
C23H25F3N4O3
CAS 号
2230836-55-0
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Michael Gmachl, et al. Novel benzylamino substituted quinazolines and derivatives as sos1 inhibitors. WO2018115380A1.
[2]. Marco H Hofmann, et al. Abstract PL06-01: Discovery of BI-3406: A potent and selective SOS1::KRAS inhibitor opens a new approach for treating KRAS-driven tumors. December 2019.
BI-882370 is a potent and selective RAF kinase inhibitor that binds to the ATP binding site of the kinase positioned in the DFG-out (inactive) conformation of the BRAF kinase. BI-882370 (BI 882370) inhibits the oncogenic BRAFV600E-mutant, the WT BRAF and CRAF kinases with IC50s of 0.4, 0.8, and 0.6 nM, respectively. BI-882370 also inhibits SRC family kinases[1].
IC50 & Target[1]
Braf
0.6 nM (IC50)
c-Raf
0.8 nM (IC50)
BRafV600E
0.4 nM (IC50)
体外研究 (In Vitro)
BI-882370 (0.9-6000 nM; 3 days) inhibits the BRAF-mutant human melanoma and colorectal cancer cells proliferation with a EC50 range of 1-10 nM[1]. BI 882370 (0.1-100 nM, 0.1-3000 nM; 2 hours) results in a reduction of p-MEK1/2, p-ERK1/2 and cyclin D1/D2 expression in BRAFV600E-mutant A375 cells; induces phosphorylation of MEK1/2 and enhanced phosphorylation of ERK1/2 in WT BRO cells (3-300 nM)[1]. BI 882370 (0.1-100 nM, 0.1-3000 nM; 24 hours) suppresses cyclin D1/D2 expression, induces Kip1/p27 expression at concentrations of 1 nM or higher in BRAFV600E-mutant A375 cells, expression of cyclins D1/D2 or Kip1/p27 is not affected in WT BRO cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
Cell Line:
BRAF-mutant and WT melanoma cell lines (A101D, A375, SK-MEL-28, G-361, and BRO); Colorectal cancer cell lines (COLO 205, HT-29, LS411N, and HCT-116)
Concentration:
0.9-6000 nM
Incubation Time:
3 days
Result:
Showed a EC50 range of 1-10 nM in an extended panel of BRAF-mutant human melanoma and colorectal cancer cell; while proliferation of BRAF WT cells was inhibited with EC50 >1 μM.
Resulted in a reduction of phospho-MEK1/2 signals and cyclin D1/D2 expression in BRAFV600E-mutant A375 cells.
体内研究 (In Vivo)
BI-882370 (deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks) is efficacious in multiple mouse models of BRAF-mutant melanomas and colorectal carcinomas, shows superior efficacy compared with Vemurafenib, Dabrafenib, or Trametinib[1]. BI-882370 (deliver orally; 25 mg/kg; twice daily; 40 days) developes resistance within 3 weeks, but resistance is not observed during 5 weeks of second-line therapy in combination with trametinib[1]. BI-882370 (deliver orally; 60 mg/kg; once daily; 2 weeks) indicates lack of toxicity in terms of clinical chemistry, hematology, pathology, and toxicogenomics in rats[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Human melanoma xenografts in nude mice with BRAF-mutant melanomas and colorectal carcinomas cells (A375, COLO 205; G-361, HT-29 cells)[1]
[1]. Waizenegger IC, et al. A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation. Mol Cancer Ther. 2016 Mar;15(3):354-65.