SNS-032 | BMS-387032 | CAS#345627-80-7 | CDK inhibitor

MedKoo Cat#: 202640 | Name: SNS-032

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SNS-032, also known as BMS-387032, is a 2-aminothiazole-derived, small-molecule cyclin dependent kinase (CDK) inhibitor with potential antineoplastic activity. CDK inhibitor SNS-032 selectively binds to CDKs 2, 7, and 9, preventing their phosphorylation and activation; inhibition of CDK activity may result in cell cycle arrest, the induction of apoptosis and decreased tumor cell proliferation in susceptible tumor cell populations. This agent has been shown to sensitize radioresistant tumor cells to ionizing radiation.

Chemical Structure

SNS-032

CAS#345627-80-7 (free base)

Theoretical Analysis

MedKoo Cat#: 202640

Name: SNS-032

CAS#: 345627-80-7 (free base)

Chemical Formula: C17H24N4O2S2

Exact Mass: 380.1341

Molecular Weight: 380.53

Elemental Analysis: C, 53.66; H, 6.36; N, 14.72; O, 8.41; S, 16.85

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 400.00	Ready to ship
100mg	USD 650.00	Ready to ship
200mg	USD 1,150.00	Ready to ship

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Related CAS #

345627-80-7 (free base) 345627-90-9 (HCl)

Synonym

SNS 032; SNS032; SNS-032; BMS387032; BMS 387032; BMS-387032

IUPAC/Chemical Name

N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide

InChi Key

OUSFTKFNBAZUKL-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H24N4O2S2/c1-17(2,3)12-8-19-13(23-12)10-24-14-9-20-16(25-14)21-15(22)11-4-6-18-7-5-11/h8-9,11,18H,4-7,10H2,1-3H3,(H,20,21,22)

SMILES Code

O=C(C1CCNCC1)NC2=NC=C(SCC3=NC=C(C(C)(C)C)O3)S2

Appearance

white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

SNS-032 selectively inhibits CDK2, CDK7, and CDK9. CDK2 and CDK7 are active in cell-cycle progression. CDK7 is also active in promoting transcription, as is CDK9. SNS-032 therefore has dual mechanisms of action-inhibiting proliferation by blocking replication, and inducing apoptosis by blocking transcription to turn off survival and growth factors. (from: http://sunesis.com/science/oncology/MOA032.php).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#SSC50330

View CoA: current batch, Lot#ZWC30715

QC Data

View QC data: current batch, Lot#SSC50330

View QC data: current batch, Lot#ZWC30715

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SNS-032 is a potent and selective inhibitor of CDK2, CDK7, and CDK9 with IC50s of 38 nM, 62 nM and 4 nM, respectively.

In vitro activity:

This study indicates that SNS-032 is a promising therapeutic agent for esophageal squamous cell carcinoma treatment. SNS-032 effectively inhibited cellular viability, abrogated anchorage-independent growth, and potentiated the sensitivity to cisplatin in ESCC cells. SNS-032 induced a mitochondrial-dependent apoptosis of ESCC cells by reducing Mcl-1 transcription and potently abrogated the abilities of ESCC cell migration and invasion through transcriptional downregulation of MMP-1. Reference: Cell Death Dis. 2021 Nov 5;12(11):1048. https://pubmed.ncbi.nlm.nih.gov/34741018/

In vivo activity:

SNS-032 is a potential drug and CDK9 might be a new prospective target for the treatment of liver fibrosis. In a mouse model of liver fibrosis, SNS-032 was found to alleviate hepatic fibrosis by inhibiting the activation and inducing the apoptosis of active hepatic stellate cells. Reference: Front Pharmacol. 2022 Oct 12;13:1016552. https://pubmed.ncbi.nlm.nih.gov/36313366/

	Solvent	mg/mL	mM
Solubility
	DMSO	42.8	112.47

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 380.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zeng H, Yang H, Song Y, Fang D, Chen L, Zhao Z, Wang C, Xie S. Transcriptional inhibition by CDK7/9 inhibitor SNS-032 suppresses tumor growth and metastasis in esophageal squamous cell carcinoma. Cell Death Dis. 2021 Nov 5;12(11):1048. doi: 10.1038/s41419-021-04344-w. PMID: 34741018; PMCID: PMC8571299. 2. Meng H, Jin Y, Liu H, You L, Yang C, Yang X, Qian W. SNS-032 inhibits mTORC1/mTORC2 activity in acute myeloid leukemia cells and has synergistic activity with perifosine against Akt. J Hematol Oncol. 2013 Feb 18;6:18. doi: 10.1186/1756-8722-6-18. PMID: 23415012; PMCID: PMC3599109. 3. He XL, Hu YH, Chen JM, Zhang DQ, Yang HL, Zhang LZ, Mu YP, Zhang H, Chen GF, Liu W, Liu P. SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via inhibition of cyclin dependent kinase 9. Front Pharmacol. 2022 Oct 12;13:1016552. doi: 10.3389/fphar.2022.1016552. PMID: 36313366; PMCID: PMC9597511. 4. Jiang L, Wen C, Zhou H, Liu A, Zhang H, Chen X, Ding W, Liu J, Shi X. Cyclin-dependent kinase 7/9 inhibitor SNS-032 induces apoptosis in diffuse large B-cell lymphoma cells. Cancer Biol Ther. 2022 Dec 31;23(1):319-327. doi: 10.1080/15384047.2022.2055421. PMID: 35332847; PMCID: PMC8959513.

In vitro protocol:

In vivo protocol:

1. He XL, Hu YH, Chen JM, Zhang DQ, Yang HL, Zhang LZ, Mu YP, Zhang H, Chen GF, Liu W, Liu P. SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via inhibition of cyclin dependent kinase 9. Front Pharmacol. 2022 Oct 12;13:1016552. doi: 10.3389/fphar.2022.1016552. PMID: 36313366; PMCID: PMC9597511. 2. Jiang L, Wen C, Zhou H, Liu A, Zhang H, Chen X, Ding W, Liu J, Shi X. Cyclin-dependent kinase 7/9 inhibitor SNS-032 induces apoptosis in diffuse large B-cell lymphoma cells. Cancer Biol Ther. 2022 Dec 31;23(1):319-327. doi: 10.1080/15384047.2022.2055421. PMID: 35332847; PMCID: PMC8959513.

1: Ali MA, Choy H, Habib AA, Saha D. SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular endothelial growth factor. Neoplasia. 2007 May;9(5):370-81. doi: 10.1593/neo.07136. PMID: 17534442; PMCID: PMC1877978. 2: Heath EI, Bible K, Martell RE, Adelman DC, Lorusso PM. A phase 1 study of SNS-032 (formerly BMS-387032), a potent inhibitor of cyclin-dependent kinases 2, 7 and 9 administered as a single oral dose and weekly infusion in patients with metastatic refractory solid tumors. Invest New Drugs. 2008 Feb;26(1):59-65. doi: 10.1007/s10637-007-9090-3. Epub 2007 Oct 16. PMID: 17938863. 3: Choong IC, Serafimova I, Fan J, Stockett D, Chan E, Cheeti S, Lu Y, Fahr B, Pham P, Arkin MR, Walker DH, Hoch U. A diaminocyclohexyl analog of SNS-032 with improved permeability and bioavailability properties. Bioorg Med Chem Lett. 2008 Nov 1;18(21):5763-5. doi: 10.1016/j.bmcl.2008.09.073. Epub 2008 Sep 24. PMID: 18842409. 4: Fan J, Fahr B, Stockett D, Chan E, Cheeti S, Serafimova I, Lu Y, Pham P, Walker DH, Hoch U, Choong IC. Modifications of the isonipecotic acid fragment of SNS-032: analogs with improved permeability and lower efflux ratio. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6236-9. doi: 10.1016/j.bmcl.2008.09.099. Epub 2008 Oct 2. PMID: 18926699. 5: Conroy A, Stockett DE, Walker D, Arkin MR, Hoch U, Fox JA, Hawtin RE. SNS-032 is a potent and selective CDK 2, 7 and 9 inhibitor that drives target modulation in patient samples. Cancer Chemother Pharmacol. 2009 Sep;64(4):723-32. doi: 10.1007/s00280-008-0921-5. Epub 2009 Jan 24. PMID: 19169685. 6: Kodym E, Kodym R, Reis AE, Habib AA, Story MD, Saha D. The small-molecule CDK inhibitor, SNS-032, enhances cellular radiosensitivity in quiescent and hypoxic non-small cell lung cancer cells. Lung Cancer. 2009 Oct;66(1):37-47. doi: 10.1016/j.lungcan.2008.12.026. Epub 2009 Feb 3. PMID: 19193471. 7: Chen R, Wierda WG, Chubb S, Hawtin RE, Fox JA, Keating MJ, Gandhi V, Plunkett W. Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45. doi: 10.1182/blood-2008-12-190256. Epub 2009 Feb 20. PMID: 19234140; PMCID: PMC2680368. 8: Ali MA, Reis A, Ding LH, Story MD, Habib AA, Chattopadhyay A, Saha D. SNS-032 prevents hypoxia-mediated glioblastoma cell invasion by inhibiting hypoxia inducible factor-1alpha expression. Int J Oncol. 2009 Apr;34(4):1051-60. doi: 10.3892/ijo_00000231. PMID: 19287962. 9: Dickson MA, Schwartz GK. Development of cell-cycle inhibitors for cancer therapy. Curr Oncol. 2009 Mar;16(2):36-43. doi: 10.3747/co.v16i2.428. PMID: 19370178; PMCID: PMC2669234. 10: Boquoi A, Chen T, Enders GH. Chemoprevention of mouse intestinal tumorigenesis by the cyclin-dependent kinase inhibitor SNS-032. Cancer Prev Res (Phila). 2009 Sep;2(9):800-6. doi: 10.1158/1940-6207.CAPR-09-0053. Epub 2009 Sep 1. PMID: 19723896; PMCID: PMC2819381. 11: Tong WG, Chen R, Plunkett W, Siegel D, Sinha R, Harvey RD, Badros AZ, Popplewell L, Coutre S, Fox JA, Mahadocon K, Chen T, Kegley P, Hoch U, Wierda WG. Phase I and pharmacologic study of SNS-032, a potent and selective Cdk2, 7, and 9 inhibitor, in patients with advanced chronic lymphocytic leukemia and multiple myeloma. J Clin Oncol. 2010 Jun 20;28(18):3015-22. doi: 10.1200/JCO.2009.26.1347. Epub 2010 May 17. PMID: 20479412; PMCID: PMC4979218. 12: Chen R, Chubb S, Cheng T, Hawtin RE, Gandhi V, Plunkett W. Responses in mantle cell lymphoma cells to SNS-032 depend on the biological context of each cell line. Cancer Res. 2010 Aug 15;70(16):6587-97. doi: 10.1158/0008-5472.CAN-09-3578. Epub 2010 Jul 27. PMID: 20663900; PMCID: PMC2929954. 13: Chen R, Guo L, Chen Y, Jiang Y, Wierda WG, Plunkett W. Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia. Blood. 2011 Jan 6;117(1):156-64. doi: 10.1182/blood-2010-01-262808. Epub 2010 Oct 22. PMID: 20971952; PMCID: PMC3037741. 14: Walsby E, Lazenby M, Pepper C, Burnett AK. The cyclin-dependent kinase inhibitor SNS-032 has single agent activity in AML cells and is highly synergistic with cytarabine. Leukemia. 2011 Mar;25(3):411-9. doi: 10.1038/leu.2010.290. Epub 2011 Jan 7. PMID: 21212792. 15: Wu Y, Chen C, Sun X, Shi X, Jin B, Ding K, Yeung SC, Pan J. Cyclin-dependent kinase 7/9 inhibitor SNS-032 abrogates FIP1-like-1 platelet-derived growth factor receptor α and bcr-abl oncogene addiction in malignant hematologic cells. Clin Cancer Res. 2012 Apr 1;18(7):1966-78. doi: 10.1158/1078-0432.CCR-11-1971. Epub 2012 Mar 23. PMID: 22447844. 16: Held JM, Britton DJ, Scott GK, Lee EL, Schilling B, Baldwin MA, Gibson BW, Benz CC. Ligand binding promotes CDK-dependent phosphorylation of ER-alpha on hinge serine 294 but inhibits ligand-independent phosphorylation of serine 305. Mol Cancer Res. 2012 Aug;10(8):1120-32. doi: 10.1158/1541-7786.MCR-12-0099. Epub 2012 Jun 5. PMID: 22669764; PMCID: PMC3950940. 17: Robak P, Robak T. A targeted therapy for protein and lipid kinases in chronic lymphocytic leukemia. Curr Med Chem. 2012;19(31):5294-318. doi: 10.2174/092986712803833371. PMID: 22830347. 18: Gallorini M, Cataldi A, di Giacomo V. Cyclin-dependent kinase modulators and cancer therapy. BioDrugs. 2012 Dec 1;26(6):377-91. doi: 10.1007/BF03261895. PMID: 22928661. 19: Meng H, Jin Y, Liu H, You L, Yang C, Yang X, Qian W. SNS-032 inhibits mTORC1/mTORC2 activity in acute myeloid leukemia cells and has synergistic activity with perifosine against Akt. J Hematol Oncol. 2013 Feb 18;6:18. doi: 10.1186/1756-8722-6-18. PMID: 23415012; PMCID: PMC3599109. 20: Qi RZ, Ji Q, Zhang LY, Zhang Y, Yuan WP, Cheng T, Gao YD, Xu J. [Effect of SNS-032 on biological activity of hematopoietic stem cells in mice]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Jun;21(3):741-5. Chinese. doi: 10.7534/j.issn.1009-2137.2013.03.040. PMID: 23815933.