BMS-986144 is a third-generation, pan-genotype (GT) NS3/4A protease inhibitor. BMS-986144 inhibits HCV replicon with EC50s of 2.3, 0.7, 1.0, 12, 8.0, and 5.8 nM for GT-1a, GT-1b, GT-2a, GT-3a, 1a R155X, and 1b D168V, respectively. BMS-986144 has the potential for the research of HCV infection[1].
分子量
856.94
Formula
C40H48D3F4N5O9S
CAS 号
1606150-08-6
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]. Sun LQ, et al. Discovery of BMS-986144, a Third-Generation, Pan-Genotype NS3/4A Protease Inhibitor for the Treatment of Hepatitis C Virus Infection [published online ahead of print, 2020 Nov 23]. J Med Chem. 2020;10.1021/acs.jmedchem.0c01296.
Trilaciclib hydrochloride (G1T28 hydrochloride) is a CDK4/6 inhibitor with IC50s of 1 nM and 4 nM for CDK4 and CDK6, respectively[1].
IC50 & Target
Cdk4/cyclin D1
1 nM (IC50)
cdk6/cyclin D3
4 nM (IC50)
体外研究 (In Vitro)
Incubation with Trilaciclib hydrochloride (G1T28) for 24 hours induces a robust G1 cell-cycle arrest (time=0). By 16 hours after Trilaciclib hydrochloride washout, cells have reentered the cell cycle and demonstrate cell-cycle kinetics similar to untreated control cells. These results demonstrate that Trilaciclib hydrochloride causes a transient, and reversible G1 arrest. A transient Trilaciclib hydrochloride-mediated G1 cell-cycle arrest in CDK4/6-sensitive cells decreases the in vitro toxicity of a variety of commonly used cytotoxic chemotherapy agents associated with myelosuppression[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)
Trilaciclib hydrochloride (G1T28) treatment results in a robust and dose-dependent suppression of proliferation in HSPCs at 12 hours, with 5-ethynyl-2′-deoxyuridine (EdU) incorporation returning near baseline levels in a dose-dependent manner by 24 hours after administration. These data demonstrate that a single oral dose of Trilaciclib hydrochloride can produce reversible cell-cycle arrest in HSPCs in a dose-dependent manner in vivo. Mice given 100 mg/kg Trilaciclib hydrochloride 30 minutes prior to etoposide treatment, exhibits only background levels of caspase-3/7 activity. These data demonstrate that Trilaciclib hydrochloride can protect the bone marrow from chemotherapy-induced apoptosis in vivo. The data demonstrate that treatment with Trilaciclib hydrochloride prior to 5-fluorouracil (5-FU) likely decreases 5-FU-induced damage by chemotherapy in HSPCs, thus accelerating blood count recovery after chemotherapy[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
519.47
Formula
C24H32Cl2N8O
CAS 号
1977495-97-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Bisi JE, et al. Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. Mol Cancer Ther. 2016 May;15(5):783-93.
Kinase Assay [1]
HS68, WM2664, and A2058 cells are treated with 300 nM Trilaciclib hydrochloride (G1T28) or DMSO (0.1%), for 4, 8, 16, or 24 hours. Whole cell extracts are prepared using 1× radioimmunoprecipitation assay buffer containing 1× HALT protease and phosphatase inhibitors. Total protein concentration is determined by using the kit, according to the manufacturer’s instructions. For Western blot analysis, protein is processed as described previously. Antibodies to total RB and β-tubulin run as a loading control are assessed[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]
HS68 cells are treated for 24 hours with Trilaciclib hydrochloride (G1T28) at 10, 30, 100, 300, 1,000, or 3,000 nM final concentration. Cells are harvested and fixed in ice-cold methanol. Fixed cells are stained with 20 μg propidium iodide, 50 μg RNAse A in PBS-CMF (calcium magnesium free) +1% BSA, Fraction V. Samples are processed on Cyan ADP Analyzer, and cell-cycle analysis is completed using software[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 Administration [1]
Female athymic nude mice are implanted with H69 cells and monitored until treatment initiation. Once tumors reach an acceptable size (150 mm3), mice are dosed in various combinations of Trilaciclib hydrochloride (G1T28) and topotecan for 5 days per week for 4 weeks. Tumors are measured for up to 60 days after treatment. All mice that reach excessive tumor burden before 60 days are humanely euthanized. Topotecan and Trilaciclib hydrochloride levels in blood plasma from the mice treated with Trilaciclib hydrochloride and/or topotecan are processed and analyzed using established methods[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]. Bisi JE, et al. Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. Mol Cancer Ther. 2016 May;15(5):783-93.
Proxalutamide (GT0918) is an orally active potent androgen receptor (AR) antagonist. Proxalutamide (GT0918) can be used in the study for prostate cancer and COVID-19[1][2][3][4][5].
IC50 & Target
Androgen Receptor[1].
体外研究 (In Vitro)
Proxalutamide (GT0918) down-regulates AR protein level in prostate cancer cells[1]. Proxalutamide can overcome the resistance of prostatic cancer cells by downregulating the expression of AR genes[4]. Proxalutamide (GT0918, 0-200 μM) dose-dependently inhibits cell viability in LNCaP and 22RV1[5].
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[5].
Cell Line:
Four human PCa cell lines, LNCaP, 22RV1, PC3 and DU145.
Concentration:
1, 2, 5, 10, 20, 50, 100, and 200 μM.
Incubation Time:
Up to 72 h.
Result:
Preferentially affected AR-positive PCa cells (IC50 values from 6.90 to 32.07 μM) over AR-negative cells (IC50 > 200 μM).
体内研究 (In Vivo)
The elimination half-life (t1/2) of proxalutamide in rats is approximately 2 h regardless of whether it is administered by the intragastric or the intravenous route. The maximum plasma concentration of proxalutamide (Cmax) could reach 2 μg/mL or higher, and the oral absolute bioavailability (F) was approximately 80%[4].
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:
Rats[4].
Dosage:
20 mg/kg (Pharmacokinetic Analysis).
Administration:
Intragastrically.
Result:
T1/2 = 2 h and F% = 80%
Clinical Trial
分子量
517.50
Formula
C24H19F4N5O2S
CAS 号
1398046-21-3
中文名称
普克鲁胺
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Youzhi Tong, et al. Abstract 614: Proxalutamide (GT0918), a potent androgen receptor pathway inhibitor. Cancer Research. AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA.
[2]. Yang M, et al. Microenvironmental pH-modified solid dispersions to enhance the dissolution and bioavailability of poorly water-soluble weakly basic GT0918, a developing anti-prostate cancer drug: preparation, characterization and evaluation in vivo. Int J Pharm. 2014 Nov 20;475(1-2):97-109.
[3]. Monitoring Editor, et al. Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial. Cureus. 2021 Feb; 13(2): e13492.
[4]. Hua Sang, et al. Quantitative determination of proxalutamide in rat plasma and tissues using liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2021 Feb 15;35(3):e9003.
[5]. Feng Qu, et al. Metabolomic profiling to evaluate the efficacy of proxalutamide, a novel androgen receptor antagonist, in prostate cancer cells. Invest New Drugs. 2020 Oct;38(5):1292-1302.
Lerociclib dihydrochloride (G1T38 dihydrochloride) is a potent and selective inhibitor of CDK4/CDK6, with IC50s of 1 nM and 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively.
IC50 & Target[1]
Cdk4/cyclin D1
1 nM (IC50)
cdk6/cyclin D3
2 nM (IC50)
CDK9/Cyclin T
28 nM (IC50)
CDK5/p35
832 nM (IC50)
Cdk5/p25
1.2 μM (IC50)
cdk2/cyclin A
1.5 μM (IC50)
CDK2/cyclinE
3.6 μM (IC50)
CDK1/cyclinB1
2.4 μM (IC50)
CDK7/Cyclin H/MAT1
2.4 μM (IC50)
体外研究 (In Vitro)
Within the CDK family, Lerocyclib is least selective against CDK9/cyclin T, ~30 fold between CDK4/cyclin D1 and CDK9/ cyclin T at the biochemical IC50. Lerociclib produces a robust and sustained G1 arrest in CDK4/6 dependent cells with an EC50 of ~20 nM. A dose dependent increase of cells in the G1 phase of the cell cycle is observed when CDK4/6 dependent WM2664 cells are treated with G1T38 for 24 hours. This arrest is maintained through 300 nM, more than 300x the biochemical IC50. WM2664 cells treated with 30-1000 nM of Lerociclib for 24 hours exhibits a complete inhibition of RB phosphorylation compared to vehicle controls. Treatment with G1T38 reduces RB phosphorylation within 1 hour post-treatment and generates near complete inhibition of RB phosphorylation by 16 hours post-treatment. G1T38 produces a robust inhibition of proliferation in a diverse array of tumor cell lines including breast, melanoma, leukemia and lymphoma with EC50 concentrations as low as 23 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.
体内研究 (In Vivo)
In this HER2+ breast cancer model, Mice treated with Lerociclib elicits 8% tumor regression after 21 days of treatment while control animals have a 577% increase in tumor burden over the same treatment period. Compared to the vehicle-treated mice, daily treatment with 100 mg/kg of Lerociclib or palbociclib shows tumor regression within 10 days in the MCF7 xenograft model. After 27 days of treatment, tumor growth inhibition is observed in the 10, 50, and 100 mg/kg Lerociclib cohorts (approximately 12%, 74%, and 90% inhibition, respectively). Daily oral palbociclib treatment causes an 18%, 66%, and 87% tumor growth inhibition in the 10, 50, and 100 mg/kg dosage cohorts, respectively. Interestingly, at 50 mg/kg, Lerociclib is significantly more efficaciou than palbociclib. Similar results are seen in the ER+ ZR-75-1 breast cancer xenograft model when comparing Lerocyclib and palbociclib at the 50 mg/kg dose. Lerociclib treated mice exhibits 77% TGI with an overall 60% tumor growth delay demonstrating Lerociclib alone is highly efficacious in this NSCLC tumor 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.
Clinical Trial
分子量
547.52
Formula
C26H36Cl2N8O
CAS 号
2097938-59-3
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Bisi JE, et al. Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors. Oncotarget. 2017 Jun 27;8(26):42343-42358.
Cell Assay [1]
SupT1, Daudi, MCF7, ZR-75-1, A2058, WM2664, and H69 cells are seeded at 1000 cells per well; MV-4-11 and BV173 cells are plated at 4000 cells per well; Tom-1 cells are plated at 8,000 cells per well; NALM-1 cells are plated at 20,000 cells per well in Costar 3903 96 well plates. After 24 hours, plates are dosed with Lerociclib at a nine-point dose concentration from 10 μM to 1 nM. Cell viability is determined after four or six days. Plates are processed on BioTek Synergy2 multi-mode plate reader and data analyzed using GraphPad Prism 5 statistical software[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 Administration [1]
Mice[1] Female MMTV-NEU mice are used to test the efficacy of Lerociclib (100 mpk, medicated diet). At time of treatment, body composition is assessed and weight measurements (in grams) are recorded and used as a measure of gross toxicity. Female nude mice are implanted with NSCLC PDX CTG0159 tumor. Mice are then randomized into treatment groups and dosing initiated once tumors reached a volume that fell within the range of 150-300 mm3. 100 mg/kg Lerociclib or vehicle is orally administered for 28 consecutive days. Female NCI Ath/nu mice are implanted with H1975 NSC lung adenocarcinoma model. Once tumors reach an average size of 100-150 mm3, mice are randomized into treatment cohorts. Mice are orally administered daily Afatinib (20 mg/kg), Erlotinib (70 mg/kg), or Lerociclib (50 or 100 mg/kg), as single agents or in combination (Lerociclib+Erlotinib or Lerociclib+Afatinib) for the duration of the study. All tumors are measured twice weekly until mice reach tumor burden of 1500 mm3.
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]. Bisi JE, et al. Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors. Oncotarget. 2017 Jun 27;8(26):42343-42358.
Rintodestrant (G1T48) is an orally active, non-steroidal and selective estrogen receptor degrader. Rintodestrant (G1T48) is also a CDK4/6 inhibitor[1].
体外研究 (In Vitro)
Rintodestrant (G1T48) is a potent and efficacious inhibitor of estrogen-mediated transcription and proliferation in ER-positive breast cancer cells, similar to the pure antiestrogen fulvestrant[1]. Rintodestrant (G1T48) selectively inhibits the growth of ER-positive, but not ER-negative, breast cancer 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 Viability Assay[1]
Cell Line:
MCF7 cells.
Concentration:
1 pM-1 μM.
Incubation Time:
18 h.
Result:
Downregulates the estrogen receptor in breast cancer cells. Significantly inhibited estrogen-mediated growth of MCF7 cells demonstrating approximately threefold higher potency when compared to Fulvestrant. Does not impact apoptosis in MCF7 breast cancer cells.
体内研究 (In Vivo)
Rintodestrant (G1T48, 30 or 100 mg/kg) inhibits estrogen signaling in endocrine-resistant breast cancer models[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:
MCF7 xenograft tumors[1].
Dosage:
30 or 100 mg/kg.
Administration:
P.O. daily for 28 days.
Result:
Demonstrated dose-dependent inhibition of TamR tumor growth.
分子量
462.49
Formula
C26H19FO5S
CAS 号
2088518-51-6
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]. Kaitlyn J Andreano, et al. G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer. Breast Cancer Res Treat. 2020 Apr;180(3):635-646.
Lerociclib (G1T38) is a potent and selective inhibitor of CDK4/6, with IC50s of 1 nM, 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively.
IC50 & Target
cdk2/cyclin A
1.5 μM (IC50)
CDK2/cyclinE
3.6 μM (IC50)
Cdk4/cyclin D1
1 nM (IC50)
cdk6/cyclin D3
2 nM (IC50)
CDK9/Cyclin T
28 nM (IC50)
CDK5/p35
0.832 μM (IC50)
CDK1/cyclinB1
2.4 μM (IC50)
CDK7/Cyclin H/MAT1
2.4 μM (IC50)
Cdk5/p25
1.2 μM (IC50)
体外研究 (In Vitro)
Within the CDK family, Lerociclib is least selective against CDK9/cyclin T, ~30 fold between CDK4/cyclin D1 and CDK9/ cyclin T at the biochemical IC50. Lerociclib produces a robust and sustained G1 arrest in CDK4/6 dependent cells with an EC50 of ~20 nM. A dose dependent increase of cells in the G1 phase of the cell cycle is observed when CDK4/6 dependent WM2664 cells are treated with Lerociclib for 24 hours. This arrest is maintained through 300 nM, more than 300x the biochemical IC50. WM2664 cells treated with 30-1000 nM of Lerociclib for 24 hours exhibits a complete inhibition of RB phosphorylation compared to vehicle controls. Treatment with Lerociclib reduces RB phosphorylation within 1 hour post-treatment and generates near complete inhibition of RB phosphorylation by 16 hours post-treatment. Lerociclib produces a robust inhibition of proliferation in a diverse array of tumor cell lines including breast, melanoma, leukemia and lymphoma with EC50 concentrations as low as 23 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.
体内研究 (In Vivo)
In this HER2+ breast cancer model, Mice treated with Lerociclib elicits 8% tumor regression after 21 days of treatment while control animals have a 577% increase in tumor burden over the same treatment period. Compared to the vehicle-treated mice, daily treatment with 100 mg/kg of Lerocyclib or palbociclib shows tumor regression within 10 days in the MCF7 xenograft model. After 27 days of treatment, tumor growth inhibition is observed in the 10, 50, and 100 mg/kg Lerociclib cohorts (approximately 12%, 74%, and 90% inhibition, respectively). Daily oral palbociclib treatment causes an 18%, 66%, and 87% tumor growth inhibition in the 10, 50, and 100 mg/kg dosage cohorts, respectively. Interestingly, at 50 mg/kg, Lerociclib is significantly more efficaciou than palbociclib. Similar results are seen in the ER+ZR-75-1 breast cancer xenograft model when comparing Lerocyclib and palbociclib at the 50 mg/kg dose. Lerociclib treated mice exhibits 77% TGI with an overall 60% tumor growth delay demonstrating Lerocyclib alone is highly efficacious in this NSCLC tumor model.
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
474.60
Formula
C26H34N8O
CAS 号
1628256-23-4
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]. Bisi JE, et al. Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors. Oncotarget. 2017 Jun 27;8(26):42343-42358.
Cell Assay
SupT1, Daudi, MCF7, ZR-75-1, A2058, WM2664, and H69 cells are seeded at 1000 cells per well; MV-4-11 and BV173 cells are plated at 4000 cells per well; Tom-1 cells are plated at 8,000 cells per well; NALM-1 cells are plated at 20,000 cells per well in Costar 3903 96 well plates. After 24 hours, plates are dosed with Lerociclib (G1T38) at a nine-point dose concentration from 10 μM to 1 nM. Cell viability is determined after four or six days. Plates are processed on BioTek Synergy2 multi-mode plate reader and data analyzed using GraphPad Prism 5 statistical software[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 Administration [1]
Mice[1] Female MMTV-NEU mice are used to test the efficacy of Lerocyclib (G1T38) (100 mpk, medicated diet). At time of treatment, body composition is assessed and weight measurements (in grams) are recorded and used as a measure of gross toxicity. Female nude mice are implanted with NSCLC PDX CTG0159 tumor. Mice are then randomized into treatment groups and dosing initiated once tumors reached a volume that fell within the range of 150-300 mm3. 100 mg/kg Lerociclib (G1T38) or vehicle is orally administered for 28 consecutive days. Female NCI Ath/nu mice are implanted with H1975 NSC lung adenocarcinoma model. Once tumors reach an average size of 100-150 mm3, mice are randomized into treatment cohorts. Mice are orally administered daily afatinib (20 mg/kg), erlotinib (70 mg/kg), or Lerociclib (50 or 100 mg/kg), as single agents or in combination (Lerociclib+erlotinib or Lerociclib+afatinib) for the duration of the study. All tumors are measured twice weekly until mice reach tumor burden of 1500 mm3.
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]. Bisi JE, et al. Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors. Oncotarget. 2017 Jun 27;8(26):42343-42358.
