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Purity: ≥98%
THAL-SNS-032 is a novel, potent and selective CDK9 degrader baed on PROTAC technology to degrade CDK9. THAL-SNS-032 is composed of a CDK-binding SNS-032 ligand linked to a thalidomide which is E3 ligase ligand that binds the E3 ubiquitin ligase Cereblon (CRBN). Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. THAL-SNS-032 induced rapid degradation of CDK9 without affecting the levels of other SNS-032 targets. Moreover, the transcriptional changes elicited by THAL-SNS-032 were more like those caused by NVP-2 than those induced by SNS-032. Notably, compound washout did not significantly reduce levels of THAL-SNS-032-induced apoptosis, suggesting that CDK9 degradation had prolonged cytotoxic effects compared with CDK9 inhibition. Thus, the findings suggest that thalidomide conjugation represents a promising strategy for converting multi-targeted inhibitors into selective degraders and reveal that kinase degradation can induce distinct pharmacological effects compared with inhibition.
| ln Vitro |
CDK9 degradation is bidirectionally induced by THAL-SNS-032 [1]. Polymerase II elongation is decreased by THAL-SNS-032[1]. With an IC50 of 50 nM, THAL-SNS-032 suppresses the growth of MOLT4 cells[1].
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| References |
[1]. Olson CM，et al. Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation. Nat Chem Biol. 2018 Feb;14(2):163-170.
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| Molecular Formula |
C40H52N8O10S2
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|---|---|
| Molecular Weight |
869.018486976624
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| CAS # |
2139287-33-3
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| Related CAS # |
345627-90-9 (HCl); 2139287-33-3 (THAL-SNS-032, a selective CDK9 degrader)
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
O=C(C1CCN(CC(NCCOCCOCCOCCNC2=CC=CC(C(N3C(CC4)C(NC4=O)=O)=O)=C2C3=O)=O)CC1)NC5=NC=C(SCC6=NC=C(C(C)(C)C)O6)S5
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| InChi Key |
BXDZOYLPNAIDOC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C40H52N8O10S2/c1-40(2,3)29-21-43-32(58-29)24-59-33-22-44-39(60-33)46-35(51)25-9-13-47(14-10-25)23-31(50)42-12-16-56-18-20-57-19-17-55-15-11-41-27-6-4-5-26-34(27)38(54)48(37(26)53)28-7-8-30(49)45-36(28)52/h4-6,21-22,25,28,41H,7-20,23-24H2,1-3H3,(H,42,50)(H,44,46,51)(H,45,49,52)
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| Chemical Name |
N-(5-(((5-(tert-Butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-(14-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-2-oxo-6,9,12-trioxa-3-azatetradecyl)piperidine-4-carboxamide
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| Synonyms |
THAL-SNS 032; THAL SNS-032; THAL-SNS032; THAL-SNS-032; THALSNS032; THAL SNS 032; THALSNS-032
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~115.07 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.88 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.88 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1507 mL | 5.7536 mL | 11.5072 mL | |
| 5 mM | 0.2301 mL | 1.1507 mL | 2.3014 mL | |
| 10 mM | 0.1151 mL | 0.5754 mL | 1.1507 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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