WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202640
CAS#: 345627-80-7 (free base)
Description: 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.
MedKoo Cat#: 202640
CAS#: 345627-80-7 (free base)
Chemical Formula: C17H24N4O2S2
Exact Mass: 380.13407
Molecular Weight: 380.53
Elemental Analysis: C, 53.66; H, 6.36; N, 14.72; O, 8.41; S, 16.85
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
|Biological target:||SNS-032 (BMS-387032) 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:||The aim of the study was to characterize the effects in vitro of SNS-032. Since there is an autocrine/paracrine stimulation of insulinlike growth factor-1 receptor (IGF-1R) in AML cells, which contribute to activation of PI3K signaling , we determined the protein expressions of IGF-1R and class I PI3K isoforms after a 6-hour exposure to increasing concentrations of SNS-032 (Figure 5A). The expression of IGF-1R and p110δ was inhibited by SNS-032 in a dose-dependent fashion. In contrast, p110α protein levels were not changed. The mRNA expression of IGF-1R and p110δ (PIK3CD) was also assessed following treatment with SNS-032 for 6 h using quantitative PCR. IGF-1R and p110δ mRNA expression were significantly inhibited by the drug (Figure 5B), suggesting posttranslational effects of SNS-032 on these target proteins. To investigate whether the suppression of IGF-1R and cell death induced by SNS-032 could be causally related, the effects of IGF-1 on SNS-032-induced cell death were examined. As shown in Figure 5C, exposure of cells to 100 ng/mL IGF-1 did not reverse SNS-032-mediated cellular inhibition. In agreement with this result, addition of IGF-1 also did not change inhibition of SNS-032 on phosphorylation of mTOR at both Ser2448 and Ser2481 even though IGF-1 alone upregulated expression of phosphor-mTOR (Figure 5D). These data supported the hypothesis that SNS-032 might directly target mTORC1/mTORC2 pathway J Hematol Oncol. 2013; 6: 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599109/|
|In vivo activity:||The in vivo antitumor effect of SNS-032 was evaluated in NOD-SCID mice bearing Omm1 xenografts subcutaneously injected. When the tumor xenografts were grown to ~ 100 mm3, the mice were randomly separated into two groups (n = 8 each) and received treatment with vehicle (PBS) or SNS-032 (15 mg/kg/day, i.p.) for 14 days. The tumor growth curve (tumor volume versus time) was significantly inhibited by SNS-032 administration (Fig. 3a). The tumor size was much smaller in SNS-032-treated group (Fig. 3b). In addition, the tumor weight was lighter in SNS-032-treated mice than vehicle-treated control ones (Fig. 3c). Furthermore, detection of proliferation marker Ki67 by IHC staining showed that the proliferation of UM cells was impaired by SNS-032 treatment (Fig. 3d). Moreover, the expression of active caspase-3 was increased in tumor tissues upon SNS-032 treatment (Fig. 3d). Cell lysates from four tumors each group were detected by Western blot analysis with the indicated antibodies. The results showed that SNS-032 inhibited the CTD phosphorylation of RNA Pol II at Ser2, 5 and 7 sites; the expression and phosphorylation at Ser127 of YAP; as well as the expression of apoptosis-related protein survivin in tumor tissues (Fig. 3e), which were consistent with the in vitro findings. No obvious side effects were observed during the treatment. Similar results were observed in MP41 PDX model which recapitulates the characteristics of human UM (Fig. 3f-j). These results demonstrate that SNS-032 inhibits the growth of UM cells in vivo. Mol Cancer. 2019; 18: 140. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745806/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
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. Zhang J, Liu S, Ye Q, Pan J. Transcriptional inhibition by CDK7/9 inhibitor SNS-032 abrogates oncogene addiction and reduces liver metastasis in uveal melanoma. Mol Cancer. 2019 Sep 16;18(1):140. doi: 10.1186/s12943-019-1070-7. PMID: 31526394; PMCID: PMC6745806. 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. Boquoi A, Chen T, Enders GH. Chemoprevention of mouse intestinal tumorigenesis by the cyclin-dependent kinase inhibitor SNS032. 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.|
|In vitro protocol:||1. Zhang J, Liu S, Ye Q, Pan J. Transcriptional inhibition by CDK7/9 inhibitor SNS-032 abrogates oncogene addiction and reduces liver metastasis in uveal melanoma. Mol Cancer. 2019 Sep 16;18(1):140. doi: 10.1186/s12943-019-1070-7. PMID: 31526394; PMCID: PMC6745806. 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.|
|In vivo protocol:||1. Zhang J, Liu S, Ye Q, Pan J. Transcriptional inhibition by CDK7/9 inhibitor SNS-032 abrogates oncogene addiction and reduces liver metastasis in uveal melanoma. Mol Cancer. 2019 Sep 16;18(1):140. doi: 10.1186/s12943-019-1070-7. PMID: 31526394; PMCID: PMC6745806. 2. Boquoi A, Chen T, Enders GH. Chemoprevention of mouse intestinal tumorigenesis by the cyclin-dependent kinase inhibitor SNS032. 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.|
1: Xie G, Tang H, Wu S, Chen J, Liu J, Liao C. The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo. Int J Oncol. 2014 Aug;45(2):804-12. doi: 10.3892/ijo.2014.2467. Epub 2014 May 26. PubMed PMID: 24865236.
2: LÃ¶schmann N, Michaelis M, Rothweiler F, Zehner R, Cinatl J, Voges Y, Sharifi M, Riecken K, Meyer J, von Deimling A, Fichtner I, Ghafourian T, Westermann F, Cinatl J Jr. Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs. Transl Oncol. 2013 Dec 1;6(6):685-96. eCollection 2013 Dec 1. PubMed PMID: 24466371; PubMed Central PMCID: PMC3890703.
3: Cihalova D, Hofman J, Ceckova M, Staud F. Purvalanol A, olomoucine II and roscovitine inhibit ABCB1 transporter and synergistically potentiate cytotoxic effects of daunorubicin in vitro. PLoS One. 2013 Dec 23;8(12):e83467. doi: 10.1371/journal.pone.0083467. eCollection 2013. PubMed PMID: 24376706; PubMed Central PMCID: PMC3871618.
4: Lemke J, von Karstedt S, Abd El Hay M, Conti A, Arce F, Montinaro A, Papenfuss K, El-Bahrawy MA, Walczak H. Selective CDK9 inhibition overcomes TRAIL resistance by concomitant suppression of cFlip and Mcl-1. Cell Death Differ. 2014 Mar;21(3):491-502. doi: 10.1038/cdd.2013.179. Epub 2013 Dec 20. PubMed PMID: 24362439; PubMed Central PMCID: PMC3921597.
5: 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. doi: 10.7534/j.issn.1009-2137.2013.03.040. Chinese. PubMed PMID: 23815933.
6: 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. PubMed PMID: 23415012; PubMed Central PMCID: PMC3599109.
7: Gallorini M, Cataldi A, di Giacomo V. Cyclin-dependent kinase modulators and cancer therapy. BioDrugs. 2012 Dec 1;26(6):377-91. doi: 10.2165/11634060-000000000-00000. Review. PubMed PMID: 22928661.
8: Robak P, Robak T. A targeted therapy for protein and lipid kinases in chronic lymphocytic leukemia. Curr Med Chem. 2012;19(31):5294-318. Review. PubMed PMID: 22830347.
9: 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. PubMed PMID: 22669764; PubMed Central PMCID: PMC3950940.
10: 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. PubMed PMID: 22447844.
11: 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. PubMed PMID: 21212792.
12: 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. PubMed PMID: 20971952; PubMed Central PMCID: PMC3037741.
13: Kruse U, Pallasch CP, Bantscheff M, Eberhard D, Frenzel L, Ghidelli S, Maier SK, Werner T, Wendtner CM, Drewes G. Chemoproteomics-based kinome profiling and target deconvolution of clinical multi-kinase inhibitors in primary chronic lymphocytic leukemia cells. Leukemia. 2011 Jan;25(1):89-100. doi: 10.1038/leu.2010.233. Epub 2010 Oct 14. PubMed PMID: 20944678.
14: 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. PubMed PMID: 20663900; PubMed Central PMCID: PMC2929954.
15: 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. PubMed PMID: 20479412.
16: 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. PubMed PMID: 19723896; PubMed Central PMCID: PMC2819381.
17: Dickson MA, Schwartz GK. Development of cell-cycle inhibitors for cancer therapy. Curr Oncol. 2009 Mar;16(2):36-43. PubMed PMID: 19370178; PubMed Central PMCID: PMC2669234.
18: 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. PubMed PMID: 19287962.
19: 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. PubMed PMID: 19234140; PubMed Central PMCID: PMC2680368.
20: 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. PubMed PMID: 19193471.
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).