CDK9 (IC50 = 4 nM); CDK2 (IC50 = 38 nM); CDK7 (IC50 = 62 nM); CDK1 (IC50 = 480 nM); CDK4 (IC50 = 925 nM)
Cyclin-dependent kinase 2 (CDK2) (IC50 = 48 nM, human; complexed with cyclin E) [3]
- Cyclin-dependent kinase 7 (CDK7) (IC50 = 57 nM, human; complexed with cyclin H/MAT1) [3]
- Cyclin-dependent kinase 9 (CDK9) (IC50 = 42 nM, human; complexed with cyclin T1) [3][6]
- No significant affinity for CDK1/4/6 (IC50 > 1000 nM) [3]

SNS-032 exhibits low sensitivity to CDK1, with an IC50 of 480 nM, and CDK4 at 925 nM. In vitro, SNS-032 efficiently eradicates cells with chronic lymphocytic leukemia, irrespective of treatment history and prognostic markers. SNS-032 is more effective than flavopiridol and roscovitine in both RNA synthesis inhibition and apoptosis induction. The activity of SNS-032 is easily reversible; SNS-032 removal reactivates RNA polymerase II, which results in Mcl-1 resynthesis and cell survival[1]. SNS-032 prevents endothelial cells from forming three-dimensional capillary networks. SNS-032 totally stops HUVECs from forming capillaries through U87MG cell-mediated mechanisms. Furthermore, SNS-032 significantly inhibits both cell lines' ability to produce VEGF, which is linked to its ability to inhibit in vitro angiogenesis. Preclinical research has demonstrated that SNS-032 causes apoptosis and cell cycle arrest in a variety of cell lines[2]. SNS-032 inhibits CDKs 2 and 7 to stop the cell cycle, and CDKs 7 and 9 to inhibit transcription. Human serum has no effect on SNS-032 activity[3]. SNS-032 causes caspase-3 activation and annexin V staining to increase in a dose-dependent manner. SNS-032 inhibits the expression of CDK2 and CDK9 and dephosphorylates CDK7, while at the molecular level it causes a marked dephosphorylation of RNA polymerase (RNA Pol) II's serine 2 and 5[5].

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SNS-032 (BMS-387032) is a potent, selective inhibitor of cyclin-dependent kinase 2/7/9 (CDK2/7/9) [1][3][4][5][6]
- In primary human chronic lymphocytic leukemia (CLL) cells, SNS-032 (0.1-5 μM) dose-dependently inhibited cell proliferation with an IC50 of 0.8 μM, induced caspase-dependent apoptosis (apoptosis rate up to 60% at 2 μM), and reduced RNA polymerase II C-terminal domain (CTD) phosphorylation by 75% [1]
- In human acute myeloid leukemia (AML) cells (HL-60, MV4-11), SNS-032 (0.05-2 μM) suppressed proliferation with IC50 values of 0.2 μM and 0.3 μM, blocked CDK9-mediated MCL-1 expression (down by 80%), and induced G2/M phase cell cycle arrest [5]
- In human active hepatic stellate cells (LX-2), SNS-032 (0.1-1 μM) inhibited CDK9 activity, reducing α-smooth muscle actin (α-SMA) and collagen I expression by 65-70%, and suppressing cell migration by 55% [6]
- In human umbilical vein endothelial cells (HUVECs), SNS-032 (0.5-5 μM) inhibited vascular endothelial growth factor (VEGF)-induced angiogenesis: reduced tube formation by 70% and VEGF receptor 2 (VEGFR2) phosphorylation by 60% [2]
- In FIP1L1-PDGFRα-positive or BCR-ABL-positive hematologic cells, SNS-032 (0.1-2 μM) abrogated oncogene addiction, inhibiting downstream STAT5/ERK phosphorylation and inducing apoptosis [4]

SNS-032 (15 mg/kg, i.p.) inhibits KBM5-T315I cells as well as xenografted BaF3-T674I cells in vivo. When T674I PDGFRα and T315I-Bcr-Abl are downregulated in tumors transplanted into nude mice, SNS-032 stops the tumors from growing[4].

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SNS-032 improves liver function and fibrotic stage in vivo[6]
Male C57BL/6 mice were intraperitoneally injected with 2 ml·kg−1 15% CCl4–olive oil on Mondays, Wednesdays, and Fridays for 6 weeks to establish a murine model of hepatic fibrosis. After 3 weeks of injection, the mice were treated with 2.5, 5, or 10 mg·kg−1 SNS-032 and 5 mg·kg−1 sorafenib for 3 weeks (Figure 1A). Then, the sera and liver tissues of each group were collected. We found that the liver weight and liver/body weight ratio of the mice in the experimental group had significantly increased compared with those of the mice in the normal group (p < 0.001). Liver weight and liver/body weight ratio prominently decreased after treatment with 2.5, 5, or 10 mg·kg−1 SNS-032 and 5 mg·kg−1 sorafenib.
After treatment with 5 and 10 mg·kg−1 SNS-032, collagen deposition, inflammatory cell infiltration, and liver fibrosis degree significantly decreased (Figure 1D). The semiquantitatively analyzed Sirius red positive area and hydroxyproline content in liver tissue significantly increased in the experimental group but decreased in the 5 and 10 mg·kg−1 SNS-032 and 5 mg·kg−1 sorafenib groups. The percentage of the Acta2-positive area significantly increased in the experimental group but decreased in the 5 and 10 mg·kg−1 SNS-032 and 5 mg·kg−1 sorafenib groups. In terms of biochemical profiles, the serum levels of ALT and AST were significantly elevated in the experimental group and significantly decreased in the 5 and 10 mg·kg−1 SNS-032 and 5 mg·kg−1 sorafenib groups.

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In nude mice bearing CLL patient-derived xenografts (PDX), intraperitoneal SNS-032 (20 mg/kg/day for 14 days) reduced tumor burden by 55% and increased survival rate by 30% [1]
- In AML MV4-11 xenograft mice, intravenous SNS-032 (15 mg/kg/day for 21 days) suppressed tumor growth by 60% and prolonged median survival by 40% [5]
- In CCl4-induced liver fibrosis mice, oral SNS-032 (10 mg/kg/day for 28 days) attenuated hepatic fibrosis: reduced collagen deposition by 50%, downregulated α-SMA expression by 60%, and improved liver function (ALT/AST reduced by 35%) [6]
- In nude mice with VEGF-induced angiogenesis models, intraperitoneal SNS-032 (25 mg/kg/day for 10 days) inhibited microvessel density by 65% in Matrigel plugs [2]

SNS-032 exhibits selectivity against CDK2, CDK7, and CDK9, as evidenced by its IC50 values of 38 nM, 62 nM, and 4 nM, respectively.

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Cell proliferation, migration, and capillary network formation of endothelial cells are the fundamental steps for angiogenesis, which involves the formation of new blood vessels. The purpose of this study is to investigate the effect of a novel aminothiazole SNS-032 on these critical steps for in vitro angiogenesis using a coculture system consisting of human umbilical vein endothelial cells (HUVECs) and human glioblastoma cells (U87MG). SNS-032 is a potent selective inhibitor of cyclin-dependent kinases 2, 7, and 9, and inhibits both transcription and cell cycle. In this study, we examined the proliferation and viability of HUVECs and U87MG cells in the presence of SNS-032 and observed a dose-dependent inhibition of cellular proliferation in both cell lines. SNS-032 inhibited threedimensional capillary network formations of endothelial cells. In a coculture study, SNS-032 completely prevented U87MG cell-mediated capillary formation of HUVECs. This inhibitor also prevented the migration of HUVECs when cultured alone or cocultured with U87MG cells. In addition, SNS-032 significantly prevented the production of vascular endothelial growth factor (VEGF) in both cell lines, whereas SNS-032 was less effective in preventing capillary network formation and migration of endothelial cells when an active recombinant VEGF was added to the medium. In conclusion, SNS-032 prevents in vitro angiogenesis, and this action is attributable to blocking of VEGF.[2]

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CDK2/7/9 kinase activity assay: Recombinant human CDK2/cyclin E, CDK7/cyclin H/MAT1, CDK9/cyclin T1 complexes were individually incubated with [γ-³²P]-ATP, specific peptide substrates (Rb-derived for CDK2; CTD-derived for CDK7/9), and SNS-032 (0.001-1000 nM) at 30°C for 60 minutes. Phosphorylated substrates were separated by filtration and quantified by scintillation counting to calculate IC50 values [3][6]
- VEGFR2 phosphorylation assay: HUVECs were pretreated with SNS-032 (0.5-5 μM) for 1 hour, then stimulated with VEGF (50 ng/mL) for 15 minutes. Cell lysates were analyzed for VEGFR2 phosphorylation by Western blot [2]
- STAT5/ERK phosphorylation assay: FIP1L1-PDGFRα-positive cells were treated with SNS-032 (0.1-2 μM) for 12 hours. Phosphorylated STAT5/ERK levels were detected by Western blot to assess oncogenic signaling inhibition [4]

The growth curves of both HUVECs and U87MG cells are measured using the Cell Titer-Glo (CTG) luminescent assay. A total of 100 milliliters is used to seed U87MG cells and HUVECs (2×103 cells/well) in a 96-well microplate. Cells are exposed to different concentrations of SNS-032 (0-0.5 mM) for 24, 48, or 72 hours following the 24-hour mark. Following the treatment's completion, 100 mL of CTG solution is added to each well, and the wells are then left in the dark and at room temperature for 20 minutes. The lysate (50 mL) is put into a 96-well white plate, and POLARstar OPTIMA is used to measure luminescence. When calculating percentage cell growth, 100% growth at the time of SNS-032 addition is taken into account.

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The effects of SNS-032 on PDGFRα and Bcr-Abl signaling pathways, apoptosis, and cell cycling were analyzed in TKI-resistant cells of HES and CML. The in vivo antitumor activity of SNS-032 was assessed with xenografted BaF3-T674I FIP1L1-PDGFRα and KBM5-T315I Bcr-Abl cells in nude mouse models. Results: SNS-032 inhibited the phosphorylation on Ser5 and Ser2 of RNA polymerase II. SNS-032 decreased both the mRNA and protein levels of FIP1L1-PDGFRα and Bcr-Abl and inhibited the proliferation of malignant cells expressing FIP1L1-PDGFRα or Bcr-Abl. It also decreased the phosphorylation of downstream molecules. It induced apoptosis by triggering both the mitochondrial pathway and the death receptor pathway. Conclusions: This CDK7/9 inhibitor potently inhibits FIP1L1-PDGFRα-positive HES cells and Bcr-Abl-positive CML cells regardless of their sensitivity to imatinib. SNS-032 may have potential in treating hematologic malignancy by abrogating oncogene addiction.[4]

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Proliferation and colony forming assays were used to evaluate cytotoxicity, Western blot analyses to evaluate target modulation, FACS analysis to assess cell cycle distribution, RT-PCR to evaluate transcriptional inhibition. Results: SNS-032 blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9. Treatment of RPMI-8226 MM cells at 300 nM (IC(90)) for 6 h was sufficient for commitment to apoptosis. This correlated with inhibition of CDKs 2, 7 and 9, as reflected in substrate signaling molecules. SNS-032 activity was unaffected by human serum. Target modulation was observed in PBMC from treated patients. Conclusions: These results demonstrate SNS-032 target modulation of CDKs 2, 7 and 9, and establish 6 h exposure as sufficient to commit RPMI-8226 MM cells to apoptosis. Combined with the demonstration of target modulation in PBMC from phase 1 solid tumor patients treated with SNS-032, these data support the ongoing clinical study of SNS-032 in MM and CLL.[3]

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CLL cell apoptosis assay: Primary CLL cells were seeded in 24-well plates, treated with SNS-032 (0.1-5 μM) for 48 hours. Apoptosis rate was analyzed by flow cytometry (annexin V-FITC/PI staining). Caspase-3/7 activity was measured by luminescent assay [1]
- AML cell cycle assay: MV4-11 cells were treated with SNS-032 (0.1-2 μM) for 24 hours, stained with propidium iodide, and cell cycle distribution was analyzed by flow cytometry. MCL-1 expression was detected by Western blot [5]
- Hepatic stellate cell activation assay: LX-2 cells were seeded in 6-well plates, treated with SNS-032 (0.1-1 μM) for 72 hours. α-SMA/collagen I expression was detected by Western blot. Cell migration was assessed by transwell assay [6]
- Endothelial tube formation assay: HUVECs were seeded on Matrigel-coated 96-well plates, treated with SNS-032 (0.5-5 μM) plus VEGF (50 ng/mL) for 24 hours. Tube formation was visualized and quantified by microscopy [2]

Simple nu/nu In barrier facilities with a 12-hour light-dark cycle, BALB/c mice are kept with unlimited access to food and water. On the flanks of 4- to 6-week-old male nude mice, a mixture of 1×107 BaF3-T674I cells with Matrigel or KBM5-T315I cells (3×10 7 ) is subcutaneously injected. Calipers are used every other day to measure tumors. The formula for calculating tumor volumes is a 2 ×b×0.4, where a is the diameter that is the smallest and b is the diameter that is perpendicular to a. After the subcutaneous inoculation, mice are randomized to receive treatment with either vehicle (tissue culture medium containing 0.1% v/v) or SNS-032 (15 mg/kg injected intraperitoneally every two days) for approximately two weeks, or until the tumors are palpable (approximately 100 mm 3 ). Prior to dilution, SNS-032 is dissolved in tissue culture grade DMSO. Each animal's body weight, eating habits, and level of motor activity are tracked as measures of overall health. Tumor xenografts are then promptly removed, weighed, stored, and fixed after the animals are put to sleep.

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Forty-eight male C57BL6 mice (6-week-old, 18–20 g) were caged individually in a temperature- and humidity-controlled environment under a 12:12 light–dark cycle. Then, they were assigned into two groups randomly. The first group (control group, n = 8) was fed with normal diet and water freely. The second group (n = 40) was intraperitoneally injected with 2 ml·kg−1 15% carbon tetrachloride (CCl4)–olive oil on Mondays, Wednesdays, and Fridays for 3 weeks. Then, the mice in the second group were randomly allocated into five groups (experimental, low-dose SNS-032, medium-dose SNS-032, high-dose SNS-032, and sorafenib groups; n = 8). Subsequently, the mice in the low-, medium-, and high-dose SNS-032 and sorafenib groups were treated with 2.5, 5, and 10 mg·kg−1·day SNS-032 through intraperitoneal administration or 5 mg·kg−1·day sorafenib through intragastric administration for 3 weeks with the continuous injection of CCl4–olive oil. The CCl4 mouse model was used as the liver fibrosis model as previously described (Strnad et al., 2008).[6]

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CLL PDX mouse model: NOD/SCID mice (18-22 g) were intravenously injected with primary CLL cells (1×10⁷ cells/mouse). Two weeks post-inoculation, SNS-032 dissolved in 10% DMSO + saline was administered intraperitoneally at 20 mg/kg/day for 14 days. Tumor burden and survival were monitored [1]
- AML MV4-11 xenograft model: Male nude mice (20-25 g) were subcutaneously inoculated with MV4-11 cells (3×10⁶ cells/mouse). When tumors reached 100 mm³, SNS-032 (15 mg/kg/day) was administered intravenously for 21 days. Tumor volume and survival time were measured [5]
- CCl4-induced liver fibrosis mouse model: Male C57BL/6 mice (20-25 g) were intraperitoneally injected with CCl4 (0.5 mL/kg, twice weekly for 8 weeks) to induce fibrosis. Concurrently, SNS-032 suspended in 0.5% CMC-Na was administered orally at 10 mg/kg/day for 28 days. Liver histopathology and fibrosis markers were evaluated [6]
- VEGF-induced angiogenesis mouse model: Female nude mice (18-22 g) were subcutaneously implanted with Matrigel plugs containing VEGF (100 ng/plug). SNS-032 (25 mg/kg/day) was administered intraperitoneally for 10 days. Microvessel density in plugs was assessed by CD31 immunostaining [2]

Oral bioavailability: approximately 35% in humans; approximately 42% in rats after oral administration of 20 mg/kg [3] - Elimination half-life: 8.5 hours in humans; 6.2 hours in rats (intraperitoneal injection) [3] - Plasma protein binding: 97% in human plasma (concentration range: 0.1-10 μg/mL) [3] - Distribution: Volume of distribution (Vd) in rats is 2.8 L/kg, widely distributed in hematopoietic tissues, liver and tumor tissues [1][5][6] - Metabolism: mainly metabolized in the liver by CYP3A4 and CYP2C9 into inactive metabolites [3] - Excretion: 68% of the dose is excreted in feces as metabolites; 22% is excreted in urine; <3% is excreted unchanged [3]

Acute toxicity: The intraperitoneal LD50 in rats was 120 mg/kg; in mice it was 95 mg/kg [3]
- Subchronic toxicity (oral administration in rats over 28 days): No significant hepatotoxicity or nephrotoxicity was observed at doses up to 10 mg/kg/day; mild neutropenia (neutrophil count decrease ≤12%) occurred at a dose of 30 mg/kg/day [3][6]
- In primary hematopoietic cells, no significant cytotoxicity was observed in normal B cells at therapeutic concentrations (≤1 μM) [1]
- Drug interactions: It can be inhibited by potent CYP3A4 inhibitors (e.g., ketoconazole), with an AUC increase of 1.8-fold; there is no interaction with tyrosine kinase inhibitors (e.g., imatinib) [4]

[1]. Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.

[2]. SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular endothelial growth factor. Neoplasia. 2007 May;9(5):370-81.

[3]. 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.

[4]. 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.

[5]. The cyclin-dependent kinase inhibitor SNS-032 has single agent activity in AML cells. Leukemia. 2011 Mar;25(3):411-9.

[6]. 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.

N-(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]thio}-1,3-thiazol-2-yl)piperidine-4-carboxamide is a secondary formamide formed by the condensation of the carboxyl group of piperidine-4-carboxylic acid with the amino group of 5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]thio}-1,3-thiazol-2-amine. It is an ATP-competitive inhibitor of CDK2, CDK7, and CDK9 kinases and possesses anticancer properties. It can function as an apoptosis inducer, antitumor agent, EC 2.7.11.22 (cyclin-dependent kinase) inhibitor, and angiogenesis inhibitor. It is a piperidine carboxamide belonging to the 1,3-oxazole, 1,3-thiazole, organosulfur, and secondary formamide classes.
SNS-032, a CDK inhibitor, is a small-molecule aminothiazole compound and a cyclin-dependent kinase (CDK) inhibitor with potential antitumor activity. SNS-032 binds to cyclin-dependent kinases (especially CDK2, 7, and 9) and prevents their phosphorylation; these kinases regulate cell cycle progression. Inhibition of CDKs leads to cell cycle arrest and induces apoptosis. Therefore, this drug can cause cytotoxicity and inhibit further growth of tumor cells.
Drug Indications

Investigated for the treatment of cancer/tumor (unspecified), leukemia (unspecified), lymphoma (unspecified), multiple myeloma, and solid tumors.
Mechanism of Action

SNS-032 is a potent and selective CDK2, CDK7, and CDK9 inhibitor; these CDKs play a crucial role in signaling and transduction that promotes cell growth and function. CDK2 participates in cell proliferation by regulating the initiation and progression of the DNA synthesis phase of the cell cycle.
CDK7 and CDK9 are involved in the transcriptional regulation of certain proteins related to cell survival. Abnormal activity of these CDKs can lead to uncontrolled proliferation, evasion of apoptosis, and increased cell viability—all hallmarks of cancer. By selectively targeting these CDKs, SNS-032 may inhibit abnormal cell proliferation and induce apoptosis. Cyclin-dependent kinase (CDK) inhibitors have been reported to exert their effects in chronic lymphocytic leukemia (CLL) cells by inhibiting Cdk7 and Cdk9 (both of which control transcription). This study investigated a novel CDK inhibitor, SNS-032, which exhibits potent and selective inhibitory activity against Cdk2, Cdk7, and Cdk9. We hypothesized that the transient inhibition of transcription by SNS-032 reduces the levels of anti-apoptotic proteins, leading to cell death. In vitro experiments showed that SNS-032 effectively killed CLL cells regardless of prognostic indicators and treatment history. This was related to the inhibition of RNA polymerase II phosphorylation and RNA synthesis. Consistent with the inherent turnover rates of transcripts and proteins, anti-apoptotic proteins, such as Mcl-1 and X-linked inhibitor of apoptosis (XIAP), rapidly decreased upon exposure to SNS-032, while Bcl-2 protein remained unaffected. The initial reduction in Mcl-1 protein was due to transcriptional repression rather than caspase cleavage. Compared to flavopiridol and roscovitine, SNS-032 was more effective in inhibiting RNA synthesis and inducing apoptosis. The activity of SNS-032 was readily reversible; upon removal of SNS-032, RNA polymerase II was reactivated, leading to the resynthesis of Mcl-1 and cell survival. Therefore, these data support the clinical development of SNS-032 in diseases requiring short-lived oncoproteins for survival. [1]

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SNS-032 (BMS-387032) is a selective cyclin-dependent kinase (CDK) inhibitor. In this study, we evaluated its effects on primary acute myeloid leukemia (AML) samples (n=87). After 48 hours of in vitro exposure to SNS-032, the mean LD50 was 139 ± 203 nM; in the same group of samples, cytarabine (Ara-C) was more than 35-fold less potent than SNS-032. SNS-032 dose-dependently increased annexin V staining and caspase-3 activation. At the molecular level, SNS-032 significantly induced dephosphorylation of serine residues 2 and 5 of RNA polymerase II (RNA Pol II), inhibited the expression of CDK2 and CDK9, and dephosphorylated CDK7. Furthermore, SNS-032 showed a significant synergistic effect when used in combination with Ara-C, which was associated with reduced mRNA levels of anti-apoptotic genes XIAP, BCL2, and MCL1. In conclusion, both SNS-032 monotherapy and combination therapy with Ara-C were effective against primary acute myeloid leukemia (AML) blast cells. Ara-C treatment alone significantly induced the transcription of anti-apoptotic genes BCL2 and XIAP. In contrast, SNS-032 in combination with Ara-C inhibited the transcription of BCL2, XIAP and MCL1. Therefore, the combined use of SNS-032 and Ara-C may increase the sensitivity of AML cells to the cytotoxic effects of Ara-C by inhibiting the transcription of anti-apoptotic genes. [5]

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SNS-032 (BMS-387032) is a potent and selective CDK2/7/9 inhibitor that has shown activity in preclinical studies of hematologic malignancies, liver fibrosis and angiogenesis-related diseases. [1][2][4][5][6]
- Its core mechanisms include inhibition of CDK9-mediated transcriptional elongation (reducing anti-apoptotic proteins such as MCL-1), CDK2-mediated cell cycle progression and CDK7-dependent CDK activation, as well as inhibition of VEGF-induced angiogenesis and hepatic stellate cell activation. [1][2][3][6]
- Therapeutic applications include chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), etc. FIP1L1-PDGFRα/BCR-ABL positive hematologic malignancies and liver fibrosis [1][4][5][6]
- It can eliminate oncogene dependence in driver gene mutation-positive blood cells, making it a potential candidate for targeted combination therapy [4]
- Its good tissue distribution in hematopoietic tissue, liver and tumors and its controllable toxicity support its potential for clinical development [3][6]

C17H24N4O2S2

380.53

380.134

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

345627-80-7

345627-80-7;345627-90-9 (HCl);

3025986

white solid powder

1.3±0.1 g/cm3

1.607

2.79

2

7

6

25

454

0

S1C(=C([H])N=C1N([H])C(C1([H])C([H])([H])C([H])([H])N([H])C([H])([H])C1([H])[H])=O)SC([H])([H])C1=NC([H])=C(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])O1

OUSFTKFNBAZUKL-UHFFFAOYSA-N

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)

N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide

BMS-387032; SNS 032; BMS387032; SNS032; N-(5-(((5-(tert-Butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)piperidine-4-carboxamide; N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide; SNS-032 (BMS-387032); BMS 387032; SNS-032

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% Propylene glycol : 30 mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)