BMS641 (BMS-209641) is a selective RARβ agonist. BMS641 has a higher affinity for RARβ (Kd, 2.5 nM) that is 100 times higher than that for RARα (Kd, 225 nM) or RARγ (Kd, 223 nM)[1].
IC50 & Target[1]
RARβ
2.5 nM (Kd)
RARα
225 nM (Kd)
RARγ
223 nM (Kd)
分子量
414.92
Formula
C27H23ClO2
CAS 号
369364-50-1
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]. Germain P, et al. Rational design of RAR-selective ligands revealed by RARbeta crystal stucture. EMBO Rep. 2004;5(9):877-882.
BMS641 (BMS-209641) is a selective RARβ agonist. BMS641 has a higher affinity for RARβ (Kd, 2.5 nM) that is 100 times higher than that for RARα (Kd, 225 nM) or RARγ (Kd, 223 nM)[1].
IC50 & Target[1]
RARβ
2.5 nM (Kd)
RARα
225 nM (Kd)
RARγ
223 nM (Kd)
分子量
414.92
Formula
C27H23ClO2
CAS 号
369364-50-1
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]. Germain P, et al. Rational design of RAR-selective ligands revealed by RARbeta crystal stucture. EMBO Rep. 2004;5(9):877-882.
BMS-986260, an immuno-oncology agent, is a potent, selective, and orally active TGFβR1 inhibitor (IC50=1.6 nM). BMS-986260 displays exquisite selectivity for TGFβR1 over its isozyme TGFβR2, as well as in a panel of more than 200 kinases examined. BMS-986260 inhibits TGFβ mediated nuclear translocation of pSMAD2/3 in MINK and NHLF cells lines with an IC50 of 350 nM and 190 nM, respectively[1].
体外研究 (In Vitro)
BMS-986260 is a highly potent TGFβR1 inhibitor in both human (Kiapp=0.8 nM) and mouse (Kiapp= 1.4 nM) biochemical assays. BMS-986260 also inhibits TGFβ induced SMAD phosphorylation in NIH3T3 cell line, primary human T cells, and mouse and human whole blood. BMS-986260 inhibits TGF-β mediated induction of regulatory T cell (Treg) by downregulation of FOXP3 expression and a repression of CD25 with an IC50 of 230 nM[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
382.78
Formula
C18H12ClFN6O
CAS 号
2001559-19-7
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]. Velaparthi U, et al. Discovery of BMS-986260, a Potent, Selective, and Orally Bioavailable TGFβR1 Inhibitor as an Immuno-oncology Agent. ACS Med Chem Lett. 2020;11(2):172-178. Published 2020 Jan 28.
BMS641 (BMS-209641) is a selective RARβ agonist. BMS641 has a higher affinity for RARβ (Kd, 2.5 nM) that is 100 times higher than that for RARα (Kd, 225 nM) or RARγ (Kd, 223 nM)[1].
IC50 & Target[1]
RARβ
2.5 nM (Kd)
RARα
225 nM (Kd)
RARγ
223 nM (Kd)
分子量
414.92
Formula
C27H23ClO2
CAS 号
369364-50-1
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]. Germain P, et al. Rational design of RAR-selective ligands revealed by RARbeta crystal stucture. EMBO Rep. 2004;5(9):877-882.
BMS-986260, an immuno-oncology agent, is a potent, selective, and orally active TGFβR1 inhibitor (IC50=1.6 nM). BMS-986260 displays exquisite selectivity for TGFβR1 over its isozyme TGFβR2, as well as in a panel of more than 200 kinases examined. BMS-986260 inhibits TGFβ mediated nuclear translocation of pSMAD2/3 in MINK and NHLF cells lines with an IC50 of 350 nM and 190 nM, respectively[1].
体外研究 (In Vitro)
BMS-986260 is a highly potent TGFβR1 inhibitor in both human (Kiapp=0.8 nM) and mouse (Kiapp= 1.4 nM) biochemical assays. BMS-986260 also inhibits TGFβ induced SMAD phosphorylation in NIH3T3 cell line, primary human T cells, and mouse and human whole blood. BMS-986260 inhibits TGF-β mediated induction of regulatory T cell (Treg) by downregulation of FOXP3 expression and a repression of CD25 with an IC50 of 230 nM[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
382.78
Formula
C18H12ClFN6O
CAS 号
2001559-19-7
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]. Velaparthi U, et al. Discovery of BMS-986260, a Potent, Selective, and Orally Bioavailable TGFβR1 Inhibitor as an Immuno-oncology Agent. ACS Med Chem Lett. 2020;11(2):172-178. Published 2020 Jan 28.
BMS-986260, an immuno-oncology agent, is a potent, selective, and orally active TGFβR1 inhibitor (IC50=1.6 nM). BMS-986260 displays exquisite selectivity for TGFβR1 over its isozyme TGFβR2, as well as in a panel of more than 200 kinases examined. BMS-986260 inhibits TGFβ mediated nuclear translocation of pSMAD2/3 in MINK and NHLF cells lines with an IC50 of 350 nM and 190 nM, respectively[1].
体外研究 (In Vitro)
BMS-986260 is a highly potent TGFβR1 inhibitor in both human (Kiapp=0.8 nM) and mouse (Kiapp= 1.4 nM) biochemical assays. BMS-986260 also inhibits TGFβ induced SMAD phosphorylation in NIH3T3 cell line, primary human T cells, and mouse and human whole blood. BMS-986260 inhibits TGF-β mediated induction of regulatory T cell (Treg) by downregulation of FOXP3 expression and a repression of CD25 with an IC50 of 230 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
382.78
Formula
C18H12ClFN6O
CAS 号
2001559-19-7
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]. Velaparthi U, et al. Discovery of BMS-986260, a Potent, Selective, and Orally Bioavailable TGFβR1 Inhibitor as an Immuno-oncology Agent. ACS Med Chem Lett. 2020;11(2):172-178. Published 2020 Jan 28.
Dasatinib carbaldehyde (BMS-354825 carbaldehyde), the Dasatinib (ABL inhibitor) based moiety, binds to IAP ligand via a linker to form SNIPER [1].
分子量
471.96
Formula
C21H22ClN7O2S
CAS 号
2112837-79-1
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]. Shibata N, et al. Development of protein degradation inducers of oncogenic BCR-ABL protein by conjugation of ABL kinase inhibitors and IAP ligands. Cancer Sci. 2017 Aug;108(8):1657-1666.
Dasatinib (BMS-354825) is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The Kis are 16 pM and 30 pM for Src and Bcr-Abl, respectively. Dasatinib inhibits Bcr-Abl and Src with IC50s of <1.0 nM and 0.5 nM, respectively[1]. Dasatinib also induces apoptosis and autophagy.
IC50 & Target[1]
Bcr-Abl
1.0 nM (IC50)
Src
0.5 nM (IC50)
lck
0.4 nM (IC50)
yes
0.5 nM (IC50)
c-kit
5.0 nM (IC50)
PDGFRβ
28 nM (IC50)
p38
100 nM (IC50)
Her1
180 nM (IC50)
Her2
710 nM (IC50)
FGFR-1
880 nM (IC50)
MEK
1700 nM (IC50)
体外研究 (In Vitro)
Dasatinib demonstrates significant activity against Bcr-Abl, Src, Lck, Yes, c-Kit, PDGFRβ, p38, Her1, Her2, FGFR-1, and MEK with IC50s of <1.0, 0.50, 0.40, 0.50, 5.0, 28, 100, 180, 720, 880, and 1700 nM, respectively[1]. Dasatinib shows antiproliferative activities aversus K562 chronic myelogenous leukemia (CML), PC3 human prostate tumor, MDA-MB-231 human breast tumor, and WiDr human colon tumor cell lines with IC50s of <1.0 nM, 9.4 nM, 12 nM, and 52 nM, respectively[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)
Dasatinib (5 mg/kg and 50 mg/kg, qd×10d, 5 on-2 off) possesses potent antitumor activity and a high safety margin in a K562 xenograft model of chronic myelogenous leukemia (CML), demonstrating complete tumor regressions and low toxicity at multiple dose levels[1]. Dasatinib (10 mg/kg) has a pharmacokinetic profile appropriate for continued advancement into in vivo efficacy studies. Dasatinib (10 mg/kg) demonstrates favorable half-lives (t1/2s) of 3.3 and 3.1 h for i.v. and oral, respectively. The oral bioavailability (Fpo) in this study is 27%[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:
Nude mice bearing K562 xenografts
Dosage:
5 mg/kg and 50 mg/kg
Administration:
Oral administration on a 5 day on and 2 day off schedule.
Result:
Showed partial tumor regressions after one treatment cycle and complete disappearance of the tumor mass by the end of drug treatment. No toxicity (animal deaths, lack of weight gain) was observed.
Animal Model:
Sprague-Dawley Rats
Dosage:
10 mg/kg (Pharmacokinetic Analysis)
Administration:
Oral and i.v.
Result:
Cmax of 13.2 and 0.5 μM for i.v. and oral, respectively.
Clinical Trial
分子量
488.01
Formula
C22H26ClN7O2S
CAS 号
302962-49-8
中文名称
达沙替尼
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Lombardo LJ, et al. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004 Dec 30;47(27):6658-61.
Ixabepilone (BMS-247550) is an orally bioavailable microtubule inhibitor, which binds to tubulin and promotes tubulin polymerization and microtubule stabilization, thereby arrests cells in the G2-M phase of the cell cycle and induces tumor cell apoptosis.
体外研究 (In Vitro)
BMS-247550 is a highly potent cytotoxic agent capable of killing cancer cells at low nanomolar concentrations and retains its antineoplastic activity against human cancers that are naturally insensitive to paclitaxel or that have developed resistance to paclitaxel[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)
BMS-247550 demonstrates antitumor activity that is superior to paclitaxel in both paclitaxel-resistant and -sensitive tumors. BMS-247550 is more efficacious than paclitaxel in all five paclitaxel-resistant tumors evaluated in this study (four human and one murine): the clinically derived paclitaxel resistant Pat-7 ovarian carcinoma, the A2780Tax ovarian carcinoma that is resistant to paclitaxel because of tubulin mutations, the HCT116/VM46 MDR colon carcinoma, the clinically derived paclitaxel-resistant Pat-21 breast carcinoma, and the murine fibrosarcoma M5076. Against three paclitaxel-sensitive human tumor xenografts, BMS-247550 produces antitumor activity equivalent to paclitaxel: A2780 human ovarian carcinoma, HCT116, and LS174T human colon carcinoma[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.
Clinical Trial
分子量
506.70
Formula
C27H42N2O5S
CAS 号
219989-84-1
中文名称
伊沙匹隆
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. John T. Hunt Discovery of Ixabepilone. Mol Cancer Ther February 2009 8; 275
Kinase Assay [1]
The potency with which BMS-247550 and paclitaxel polymerize tubulin isolated from calf brain is evaluated by Published techniques. Briefly, different concentrations of paclitaxel or BMS-247550 in polymerization buffer [0.1 M mes, 1 mM EGTA, 0.5 mM MgCl2 (pH 6.6)] are added to tubulin in polymerization buffer at 37°C in microcuvette wells of a Beckman. Model DU 7400 UV spectrophotometer. A final microtubule protein concentration of 1.0 mg/mL and compound concentrations of generally 2.5, 5.0, and 10 μM are used. Initial slopes of absorbance (A280 nM) change, measured every 10 s, are calculated by the software program accompanying the instrument.
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]
HCT116 cells from cultures are collected by trypsinization after 1, 2, 4, 8, 16, and 24 h exposure to 7.5 nm of BMS-247550. Cells are pelleted and fixed in 80% ethanol at −20°C. After an overnight storage at −20°C, cells are rehydrated with PBS buffer and DNA stain by incubation with propidium iodide (5 μg/mL) in 0.1% RNase for 15-30 min. Fluorescence-activated cell sorter acquisition is performed using the FACS Calibur instrument and analysis is done using Cellquest and Modfit software.
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]. John T. Hunt Discovery of Ixabepilone. Mol Cancer Ther February 2009 8; 275
Dapagliflozin (BMS-512148), a new type of drug used to treat diabetes mellitus (DM), is a competitive sodium/glucose cotransporter 2 (SGLT2) inhibitor, which results in excretion of glucose into the urine[1]. Dapagliflozin induces HIF1 expression and attenuates renal IR injury[2].
IC50 & Target
SGLT2[1]
体外研究 (In Vitro)
Dapagliflozin (0-10 μM；24 hours) significantly increases the cell survival in hypoxic HK2 cell in a dose-dependent manner[2].Dapagliflozin (0-10 μM；2 hours) increases the HIF1 expression, increases AMPK and EKR phosphorylation in hypoxic HK2 cells, but shows no effect on the phosphorylation of AMPK and ERK in normoxic HK2 cells[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.
Cell Viability Assay[1]
Cell Line:
Hypoxic HK2 cells
Concentration:
0 μM, 1 μM, 2 μM, 5 μM, 10 μM
Incubation Time:
24 hours
Result:
Improved the cell viability in a dose-dependent manner compared with control cells.
Western Blot Analysis[1]
Cell Line:
Hypoxic HK2 cells, Normoxic HK2 cells
Concentration:
0 μM, 1 μM, 2 μM, 5 μM, 10 μM
Incubation Time:
24 hours
Result:
Induced HIF1 expression in hypoxic and normoxic HK2 cells.
体内研究 (In Vivo)
Dapagliflozin (oral administration; 10 mg/kg) causes a marked increase in urinary glucose in SGLT2i-mice, suppresses BAT thermogenesis by reducing sympathetic nerve activity and enhances hepatic gluconeogenesis and glycogenolysis[3].
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.
Clinical Trial
分子量
408.87
Formula
C21H25ClO6
CAS 号
461432-26-8
中文名称
达格列净；达帕格列净；达格列嗪
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Pedersen MG, et al. Dapagliflozin stimulates glucagon secretion at high glucose: experiments and mathematical simulations of human A-cells. Sci Rep. 2016 Aug 18;6:31214.
[2]. Chiba Y, et al. Dapagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, Acutely Reduces Energy Expenditure in BAT via Neural Signals in Mice. PLoS One. 2016 Mar 10;11(3):e0150756.
BMS-1166-N-piperidine-COOH, the BMS-1166-based moiety, binds to E3 ligase ligand via a linker to form PROTAC PD-1/PD-L1 degrader-1 (HY-131183) to degrade PD-1/PD-L1[1]. BMS-1166 is a potent PD-1/PD-L1 interaction inhibitor with an IC50 of 1.4 nM. BMS-1166 antagonizes the inhibitory effect of PD-1/PD-L1 immune checkpoint on T cell activation[2].
分子量
639.14
Formula
C37H35ClN2O6
CAS 号
2447066-00-2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
-20°C, sealed storage, away from moisture and light
*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
参考文献
[1]. Binbin Cheng, et al. Discovery of Novel Resorcinol Diphenyl Ether-Based PROTAC-like Molecules as Dual Inhibitors and Degraders of PD-L1. Eur J Med Chem. 2020 Aug 1;199:112377.
[2]. Guzik K, et al. Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1. J Med Chem. 2017 Jul 13;60(13):5857-5867.
Dapagliflozin D5 (BMS-512148 D5) is a deuterium labeled Dapagliflozin. Dapagliflozin is a competitive SGLT2 inhibitor[1].
分子量
413.90
Formula
C21H20D5ClO6
CAS 号
1204219-80-6
中文名称
达格列净 d5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
参考文献
[1]. Pedersen MG, et al. Dapagliflozin stimulates glucagon secretion at high glucose: experiments and mathematical simulations of human A-cells. Sci Rep. 2016 Aug 18;6:31214.
BMS-1 is an inhibitor of the PD-1/PD-L1 protein/protein interaction (IC50 between 6 and 100 nM)[1][2].
IC50 & Target
PD1-PDL1[1]
体外研究 (In Vitro)
Since PD-1 mediated the exhaustion of natural killer (NK) cell by binding to its ligand PD-L1, BMS-1 (PD-1/PD-L1 inhibitor 1) (1 μM, 3 days) is used to disturb the interaction between PD-1 and PD-L1. Dexamethasone induced increase of PD-1 expression and decrease of cytotoxicity of the co-cultured NK92 cells are reversed by BMS-1[1]. BMS-1, a small-molecule immune checkpoint inhibitor of PD-1/PD-L1, can be used as a therapeutic strategy for tumor immunotherapy[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.
Cell Cytotoxicity Assay[1]
Cell Line:
NK cells and HepG2 cells
Concentration:
1 μM
Incubation Time:
3 days
Result:
Disturbed the interaction between PD-1 and PD-L1.
体内研究 (In Vivo)
BMS-1 (500 μg/mL; 100 μL; i.p.) significantly increases the survival rates of the mVEGF165b group and mVEGF165b + MUC1 group[3].
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:
BALB/c mice with EMT6 cells[3]
Dosage:
500 μg/mL; 100 μL
Administration:
I.p.
Result:
Increased the survival rates of the mVEGF165b group and mVEGF165b + MUC1 group. mVEGF165b combined with MUC1 results significant retardation of the tumor growth.
分子量
475.58
Formula
C29H33NO5
CAS 号
1675201-83-8
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
Methanol : 25 mg/mL (52.57 mM; Need ultrasonic)
DMSO : 17.86 mg/mL (37.55 mM; ultrasonic and warming and heat to 60°C)
[1]. Zhao Y, et al. Depression Promotes Hepatocellular Carcinoma Progression through a Glucocorticoids Mediated Up-Regulation of PD-1 Expression in Tumor infiltrating NK Cells. Carcinogenesis. 2019 Feb 4.
[2]. Li K, et al. Development of small-molecule immune checkpoint inhibitors of PD-1/PD-L1 as a new therapeutic strategy for tumour immunotherapy. J Drug Target. 2019 Mar;27(3):244-256.
[3]. Zhang H, et al. Utilizing VEGF165b mutant as an effective immunization adjunct to augment antitumor immune response. Vaccine. 2019 Apr 3;37(15):2090-2098.
[4]. Mengyuan Li, et al. KALRN mutations promote antitumor immunity and immunotherapy response in cancer. J Immunother Cancer. 2020 Oct;8(2):e000293.
BMS-906024 is an orally active and selective γ-secretase (gamma secretase) inhibitor. BMS-906024 is a potent pan-Notch receptors inhibitor with IC50s of 1.6 nM, 0.7 nM, 3.4 nM, and 2.9 nM for Notch1, -2, -3, and -4 receptors, respectively. BMS-906024 demonstrates broad-spectrum antineoplastic activity[1][2].
BMS-906024 (5-100 nM; 72 hours) reduces Notch1 ICD levels in all six lung cancer cell lines. BMS-906024 at 100 nM, has no effect on total Notch1, and down-regulated Hes1 transcript[1]. In cancer cell proliferation assays, BMS-906024 inhibits both leukemia (TALL-1) and triple-negative breast cancer (MDA-MB-468) cells with IC50 of ∼4 nM[2]. BMS-906024 (100 nM; for 72 hours) enhances the anti-tumor activity of Paclitaxel in vitro[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.
Reduced Notch1 ICD levels in all six lung cancer cell lines tested at concentrations as low as 5 nM, with maximal depletion at 50-100 nM.
体内研究 (In Vivo)
BMS-906024 (8.5 mg/kg; oral gavage; days 1 through 4 of each week for 3 weeks) significantly enhances the tumor growth inhibition of Paclitaxel (36 mg/kg). BMS-906024 enhances Paclitaxel-mediated cytotoxicity in vivo in NSCLC through a combination of inhibiting proliferation and promoting apoptosis, in a p21 and p57-independent manner[1]. BMS-906024 has a T1/2 of 4.6/5.3 hours, a Cmax of 1/0.3 μM and an AUC of 3.4/1.9 μM•hour for IV/PO[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.
Animal Model:
Six to 12-week-old female NOD scid gamma (NSG) mice with KRAS- and BRAF-WT PDX-T42 xenografts[1]
Dosage:
8.5 mg/kg
Administration:
oral gavage; days 1 through 4 of each week for 3 weeks
Result:
Significantly enhanced the tumor growth inhibition of Paclitaxel (36 mg/kg), but had no significant effect on Cisplatin (2 mg/kg) treatment.
Animal Model:
Mouse[2]
Dosage:
1 mg/kg (Pharmacokinetic Analysis)
Administration:
IV or PO
Result:
Had a T1/2 of 4.6/5.3 hours, a Cmax of 1/0.3 μM and an AUC of 3.4/1.9 μM•hour for IV/PO.
Clinical Trial
分子量
556.50
Formula
C26H26F6N4O3
CAS 号
1401066-79-2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Morgan KM, et al. Gamma Secretase Inhibition by BMS-906024 Enhances Efficacy of Paclitaxel in Lung Adenocarcinoma. Mol Cancer Ther. 2017 Dec;16(12):2759-2769.
[2]. Gavai AV, et al. Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors. ACS Med Chem Lett. 2015 Mar 11;6(5):523-7.
BMS-5 (LIMKi 3) is a potent LIMK inhibitor with IC50s of 7 nM and 8 nM for LIMK1 and LIMK2, respectively.
IC50 & Target[1]
LIMK1
7 nM (IC50)
LIMK2
8 nM (IC50)
体外研究 (In Vitro)
BMS-5 (LIMKi 3) inhibits cofilin-Ser3 phosphorylation in a dose-dependent manner in Nf2ΔEx2 mouse Schwann cells (MSCs) with an IC50 of ~2 µM. BMS-5 (LIMKi 3) reduces Nf2ΔEx2 MSC viability in a dose-dependent manner with an IC50 of 3.9 µM, but does not significantly reduce the viability of control Nf2flox2/flox2 MSCs at equivalent BMS-5 concentrations. At 10 µM BMS-5, Nf2ΔEx2 MSC viability is 40% compared to 83% for controls[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.
体内研究 (In Vivo)
BMS-5 (LIMKi 3) (20 or 200 μM/side) is bilaterally infused into the hippocampus of rats immediately after contextual fear conditioning training. Rats are tested for memory consolidation 48 h after fear conditioning. Post hoc analysis shows that the group treated with 200 μM BMS-5 express lower freezing levels compared to the 20 μM and vehicle groups (P<0.01)[3].
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
431.29
Formula
C17H14Cl2F2N4OS
CAS 号
1338247-35-0
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Ross-Macdonald P, et al. Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors. Mol Cancer Ther. 2008 Nov;7(11):3490-8.
[2]. Petrilli A, et al. LIM Domain Kinases as Potential Therapeutic Targets for Neurofibromatosis Type 2.Oncogene. Oncogene. 2014 Jul 3;33(27):3571-82.
[3]. Lunardi P, et al. Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction. Mol Neurobiol. 2017 Jan 13.
Kinase Assay [1]
The protein kinase domains of human LIMK1 and LIMK2 are expressed as glutathione S-transferase fusion proteins using the Bac-to-Bac system in Sf9 cells. Compounds 1 to 6 (e.g., BMS-5) are assayed for inhibition of LIMK1 and LIMK2 protein kinase activity by radioactive phosphate incorporation into biotinylated full-length human destrin. Reactions are done with a concentration series of compound in 25 mM HEPES, 100 mM NaCl, 5 mM MgCl2, 5 mM MnCl2, 1 μM total ATP, 83 μg/mL biotinylated destrin, 167 ng/mL glutathione S-transferase-LIMK1, or 835 ng/mL glutathione S-transferase-LIMK2 in a total volume of 60 μL at room temperature for 30 min (LIMK1) or 60 min (LIMK2). Reactions are terminated by addition of 140 μL of 20% TCA/100 mM sodium pyrophosphate, and the precipitates are harvested onto GF/C unifilter plates. The radioactivity incorporated is determined using a TopCount after addition of 35 μL Microscint scintillation fluid[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 [2]
Cell membrane asymmetry is measured. Nf2ΔEx2 MSCs plated in a 6-well format are incubated with 2 µM BMS-5 or DMSO vehicle for 24 hrs. Cell are harvested and assayed. Plasma membrane asymmetry is evaluated with the Violet ratiometric assay by flow cytometry[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.
Animal Administration [3]
Rats [3] Male Wistar rats (age 2-3 months, weight 290-350 g) are used. BMS-5 is prepared in a vehicle solution (1% DMSO in sterile isotonic saline). At the time of infusion, a 30-gauge infusion needle is fitted into a guide cannula, with its tip protruding 1.0 mm beyond the guide cannula end and aimed at the pyramidal cell layer of CA1 of the dorsal hippocampus. Avolume of 1 μL of BMS-5 (20 and 200 μM) or vehicle (DMSO 1%) is bilaterally infused in a time of 90 s. The doses of BMS-5 are based on its IC50 value and in vitro studies.
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]. Ross-Macdonald P, et al. Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors. Mol Cancer Ther. 2008 Nov;7(11):3490-8.
[2]. Petrilli A, et al. LIM Domain Kinases as Potential Therapeutic Targets for Neurofibromatosis Type 2.Oncogene. Oncogene. 2014 Jul 3;33(27):3571-82.
[3]. Lunardi P, et al. Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction. Mol Neurobiol. 2017 Jan 13.
N-deacetylated BMS-202 is the deacetylated of BMS-202. BMS-202 is an inhibitor of the PD-1/PD-L1 interaction, mainly used for cancer treatment.
体外研究 (In Vitro)
BMS-202 inhibits PD-1/PD-Ll interaction, and may augment therapeutic immune response to a number of histologically distinct tumors. Blockade of the PD-1/PD-Ll ligation using antibodies to PD-Ll has been shown to restore and augment T cell activation in many systems[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
377.48
Formula
C23H27N3O2
CAS 号
2310135-18-1
运输条件
Room temperature in continental US; may vary elsewhere.
BMS-1001 hydrochloride is an orally active human PD-L1/PD-1 immune checkpoint inhibitor. BMS-1001 hydrochloride exhibits low-toxicity in cells[1].
IC50 & Target
PD-L1/PD-1[1].
体外研究 (In Vitro)
BMS-1001 binds to human PD-L1 and blocks its interaction with PD-1. BMS-1001 presents low toxicity towards tested cell lines and block the interaction of soluble PD-L1 with the cell surface-expressed PD-1. BMS-1001 alleviates the inhibitory effect of the soluble PD-L1 on the T-cell receptor-mediated activation of T-lymphocytes[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
631.11
Formula
C35H35ClN2O7
CAS 号
2113650-04-5
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]. Skalniak L, et al. Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells. Oncotarget. 2017 Aug 7;8(42):72167-72181.
BMS-202 is a potent and nonpeptidic PD-1/PD-L1 complex inhibitor with an IC50 of 18 nM and a KD of 8 μM. BMS-202 binds to PD-L1 and blocks human PD-1/PD-L1 interaction. BMS-202 has antitumor activity[1][2].
BMS-202 (0-100 μM; 4 days; SCC-3 or Jurkat cells) treatment inhibits the proliferation of strongly PD-L1-positive SCC-3 cells (IC50 of 15 μM) and anti-CD3 antibody-activated Jurkat cells (IC50 10 μM) in vitro[2]. BMS-202 selectively induces thermal stabilization of PD-L1. BMS-202 induces dimerization of PD-L1 in solution.BMS-202 is located at the center of the homodimer filling a deep hydrophobic pocket contributing multiple additional interactions between the monomers. BMS-202 interacts with both PD-L1 molecules using hydrophobic surfaces physiologically involved in the PD-1/PD-L1 interaction[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[2]
Cell Line:
SCC-3 or Jurkat cells
Concentration:
0-100 μM
Incubation Time:
4 days
Result:
Inhibited the proliferation of strongly PD-L1-positive SCC-3 cells (IC50 of 15 μM) and anti-CD3 antibody-activated Jurkat cells (IC50 10 μM) in vitro.
体内研究 (In Vivo)
BMS-202 (20 mg/kg; intraperitoneal injection; daily; for 9 days; NOG-dKO mice) treatment shows a clear antitumor effect compared with the controls, in humanized MHC- dKO NOG mice[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.
Animal Model:
NOG-dKO mice (8-week-old) injected with SCC-3 cells[2]
Dosage:
20 mg/kg
Administration:
Intraperitoneal injection; daily; for 9 days
Result:
Showed 41% growth inhibitory activity against humanized mouse-transplanted human lymphoma SCC-3 cells.
分子量
419.52
Formula
C25H29N3O3
CAS 号
1675203-84-5
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Zak KM, et al. Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1). Oncotarget. 2016 May 24;7(21):30323-35.
[2]. Ashizawa T, et al. Antitumor activity of the PD-1/PD-L1 binding inhibitor BMS-202 in the humanized MHC-double knockout NOG mouse. Biomed Res. 2019;40(6):243-250.
BMS-1166 is a potent PD-1/PD-L1 immune checkpoint inhibitor. BMS-1166 induces dimerization of PD-L1 and blocks its interaction with PD-1, with an IC50 of 1.4 nM. BMS-1166 antagonizes the inhibitory effect of PD-1/PD-L1 immune checkpoint on T cell activation[1][2].
IC50 & Target
IC50: 1.4 nM (PD-1/PD-L1 interaction)[1].
体外研究 (In Vitro)
BMS-1166 is a potent PD-1/PD-L1 interaction inhibitor with an IC50 of 1.4 nM in a homogenous time-resolved fluorescence binding assay[1]. BMS-1166 antagonizes the inhibitory effect of PD-1/PD-L1 immune checkpoint on T cell activation. BMS-1166 dose dependently abolishes the inhibition of ECs stimulation by sPD-L1[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
641.11
Formula
C36H33ClN2O7
CAS 号
1818314-88-3
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Guzik K, et al. Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1. J Med Chem. 2017 Jul 13;60(13):5857-5867.
[2]. Skalniak L, et al. Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells. Oncotarget. 2017 Aug 7;8(42):72167-72181.
BMS-911543 is a selective JAK2 inhibitor, with IC50s of 1.1 nM, less selective at JAK1, JAK3 and TYK2 (IC50, 75, 360, 66 nM, respectively).
IC50 & Target
JAK2
1.1 nM (IC50)
Tyk2
66 nM (IC50)
JAK1
75 nM (IC50)
JAK3
360 nM (IC50)
体外研究 (In Vitro)
BMS-911543 is a selective JAK2 inhibitor, with IC50s of 1.1 nM, less selective at JAK1, JAK3 and TYK2 (IC50, 75, 360, 66 nM, respectively). BMS-911543 displays IC50 of >25 μM for all targets except PDE4 (IC50, 5.6 μM). BMS-911543 exhibits potent antiproliferative effect on the SET-2 and BaF3-V617F engineered cell lines (both dependent upon JAK2 pathway), with IC50s of 60 and 70 nM, respectively, and such an effect on SET-2 and BaF3-V617F cells is correlated with similar activity on constitutively active pSTAT5 (IC50, 80 and 65 nM, respectively)[1]. BMS-911543 (>20 μM) is cytotoxic to murine or human pancreatic ductal adenocarcinoma (PDAC) cell lines. BMS-911543 (5 and 10 μM) also blocks T regulatory cell differentiation in vitro[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.
体内研究 (In Vivo)
BMS-911543 is well tolerated up to 100 mg/kg in rats (mean AUC0-72 h, 11300 μM·h) and dogs (AUC0-24 h, 610 μM·h). A 15 mg/kg/day dose (Day 14 AUC0-24 h, 3200 μM·h) is well tolerated[1] in two-week repeat dose studies in rats. BMS-911543 (30 mg/kg, p.o.) suppresses the growth of tumor and prolongs the median survival in KPC-Brca1 mice. BMS-911543 also selectively reduces pSTAT5 expression in pancreatic tumors and decreases levels of intratumoral FoxP3+ T regulatory cells in mice administered BMS-911543[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.
Clinical Trial
分子量
432.52
Formula
C23H28N8O
CAS 号
1271022-90-2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Wan H, et al. Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms. ACS Med Chem Lett. 2015 Jul 12;6(8):850-5.
[2]. Mace TA, et al. Single agent BMS-911543 Jak2 inhibitor has distinct inhibitory effects on STAT5 signaling in genetically engineered mice with pancreatic cancer. Oncotarget. 2015 Dec 29;6(42):44509-22.
Cell Assay [2]
Human and murine pancreatic ductal adenocarcinoma (PDAC) tumor cells or PSC are cultured in 96 well plates and the following day treated with BMS-911543 or DMSO vehicle control for 48 hours. After 48 hours, MTT reagent (ATCC) is added for 2 hours at 37°C. Samples are analyzed on a plate reader testing for absorbance at 450 nM[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.
Animal Administration [2]
Mice[2] Pancreatic tumors are confirmed in KPC-Brca1 mice by bioluminescent imaging (BLI) at 5-6 weeks of age. Briefly, mice are maintained on isofluorane anesthesia and imaged 10-15 minutes following intraperitoneal injection of Luciferin on a heated platform. Animals with a pancreatic mass of approximately 50-100 mm3 are randomized, and treatment is initiated the day following imaging. Mice are then treated for 2 weeks by daily oral gavage at a dose of 30 mg/kg BMS-911543. Following 2 weeks of treatment, animals are euthanized via CO2 asphyxiation followed by cardiac puncture. Plasma, splenocytes and tumor tissue are collected for further analysis. Pathology is assessed by H&E to determine differentiation state of the tissue as PanIN, papillary carcincoma or PDAC. For long term in vivo experiments, 8 week old KPC-Brca1 mice with advanced disease are continuously treated by oral gavage at 30 mg/kg of BMS-911543 until mice meet specified early removal criteria[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.
参考文献
[1]. Wan H, et al. Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms. ACS Med Chem Lett. 2015 Jul 12;6(8):850-5.
[2]. Mace TA, et al. Single agent BMS-911543 Jak2 inhibitor has distinct inhibitory effects on STAT5 signaling in genetically engineered mice with pancreatic cancer. Oncotarget. 2015 Dec 29;6(42):44509-22.
