2250025-88-6
2250025-88-6 structure
- Name: TL 12-186
- Chemical Name: TL12-186
- CAS Number: 2250025-88-6
- Molecular Formula: C44H51ClN10O9S
- Molecular Weight: 931.46
- Catalog: Signaling Pathways Cell Cycle/DNA Damage CDK
- Create Date: 2020-08-07 12:57:21
- Modify Date: 2024-01-14 20:16:08
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TL12-186 is a CRBN-dependent multi-kinase PROTAC degrader. Multi-kinases include CDK, BTK, FLT3, Aurora kinases, TEC, ULK, ITK, et al. TL12-186 inhibits CDK2/cyclin A (IC50=73 nM) and CDK9/cyclin T1 (IC50=55 nM)[1].
| Name | TL12-186 |
|---|
| Description | TL12-186 is a CRBN-dependent multi-kinase PROTAC degrader. Multi-kinases include CDK, BTK, FLT3, Aurora kinases, TEC, ULK, ITK, et al. TL12-186 inhibits CDK2/cyclin A (IC50=73 nM) and CDK9/cyclin T1 (IC50=55 nM)[1]. |
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| Related Catalog | |
| Target |
Cereblon cdk2/cyclin A:73 nM (IC50) CDK9/cyclinT1:55 nM (IC50) |
| In Vitro | TL12-186 displays >90% inhibition of 193 kinases at a screening concentration of 1 μM[1]. TL12-186 displays potent binding to CRBN (IC50=12 nM) using an AlphaScreen engagement assay[1]. TL12-186 (1-10000 nM; 2 days) exhibits a CRBN-dependent pharmacological effect, displaying 13 to 15-fold more potent inhibition of survival of the WT cells than the CRBN-/- cells[1]. TL12-186 (10-10000 nM; 4 hours) inhibits STAT1 phosphorylation without causing JAK1/2 degradation[1]. Cell Proliferation Assay[1] Cell Line: WT and CRBN-/- MOLM-14 cells; WT and CRBN-/- MOLT-4 cells Concentration: 1, 10, 100, 1000, 10000 nM Incubation Time: 2 days Result: Exhibited a CRBN-dependent pharmacological effect, displaying 13 to 15-fold more potent inhibition of survival of the WT cells than the CRBN-/- cells. Western Blot Analysis[1] Cell Line: MOLT-4 cells Concentration: 10, 100, 1000, 10000 nM Incubation Time: 4 hours Result: Inhibited IFN-γ (10 ng/mL)-stimulated STAT1 phosphorylation (Y701) without causing degradation of JAK1 or JAK2. |
| References |
| Molecular Formula | C44H51ClN10O9S |
|---|---|
| Molecular Weight | 931.46 |
| Hazard Codes | Xi |
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