SNS-032 Chemical Properties

Melting point:

171-173 °C

Density 

1.28±0.1 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

7.33±0.70(Predicted)

color 

White to Off-White

Safety Information

HS Code 

29349990

SNS-032 Usage And Synthesis

Description

Cyclin-dependent kinases (CDKs) are key regulators of cell cycle progression and are therefore promising targets for cancer therapy. SNS-032 is an ATP-competitive inhibitor of Cdk9, 2, and 7 with IC₅₀ values of 4, 38, and 62 nM, respectively. It is selective for these kinases and displays no additional activity against a panel of 190 kinases (IC₅₀s = >1,000 nM). SNS-032 can block the cell cycle, inhibit transcription, and induce apoptosis in multiple myeloma RPMI-8226 cells with an IC₉₀ value of 0.3 μM. This compound has been shown to induce apoptosis by inhibiting the transcription of the anti-apoptotic proteins, Mcl-1 and XIAP.

Chemical Properties

Off-White Solid

Uses

SNS 032 is a selective inhibitor of Cyclin-dependent Kinase (CDK) 2,7, and 9.

Definition

ChEBI: N-(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)piperidine-4-carboxamide is a secondary carboxamide resulting from the formal condensation of the carboxy group of piperidine-4-carboxylic acid with the amino group of 5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-amine. It is an ATP-competitive inhibitor of CDK2, CDK7 and CDK9 kinases and exhibits anti-cancer properties. It has a role as an apoptosis inducer, an antineoplastic agent, an EC 2.7.11.22 (cyclin-dependent kinase) inhibitor and an angiogenesis inhibitor. It is a piperidinecarboxamide, a member of 1,3-oxazoles, a member of 1,3-thiazoles, an organic sulfide and a secondary carboxamide.

Synthesis

Step Ih: 4-[[5-[[(5-tert-butyloxazol-2-yl)methyl]thio]thiazol-2-yl]carbamoyl]piperidine-1-carboxylic acid tert-butyl ester (Compound 0109, 1.0 g, 2 mmol) was dissolved in dichloromethane (20 ml) and trifluoroacetic acid (TFA, 2 ml) was added. The reaction mixture was stirred at 30°C for 3 hours. After completion of the reaction, the pH of the mixture was adjusted to 7-8 with saturated sodium bicarbonate solution and subsequently extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and concentrated to afford N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)piperidine-4-carboxamide (Compound 0110, 620 mg, 82% yield). Product characterization data: melting point 178.5-180 °C, LCMS m/z 381 [M + 1]+, 1H NMR (CDCl3) δ 1.164 (s, 9H), 1.720-1.795 (m, 2H), 1.923-1.969 (m, 2H), 2.714-2.777 (m, 1H), 2.889 (t, J = 12Hz , 2H), 3.281 (s, 1H), 4.046 (s, 1H), 6.708 (s, 1H), 7.393 (s, 1H), 8.844 (m, 1H).

storage

Store at -20°C

References

[1]. tong w.g., chen r., plunkett w., et al. 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. journal of clinical oncology, 2010, 28(18):3015- 3022.
[2]. chipumuro e., marco e., christensen c.l., et al. cdk7 inhibition suppresses super-enhancer-linked oncogenic transcription in mycn-driven cancer. cell, 2014, 159:1-14.
[3]. meng h., jin y.m., liu h., et al. sns-032 inhibits mtorc1/mtorc2 activity in acute myeloid leukemia cells and has synergistic activity with perifosine against akt. journal of hematology & oncology, 2013, 6:18.
[4]. chen r., wierda w.g., chubb s., et al. mechanism of action of sns032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. blood, 2009, 113(19):4637-4645.

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