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
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].
Related Catalog	Research Areas >> Cancer Signaling Pathways >> Cell Cycle/DNA Damage >> CDK Signaling Pathways >> PROTAC >> PROTAC
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	[1]. Hai-Tsang Huang, et al. A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader. Cell Chem Biol. 2018 Jan 18;25(1):88-99.e6.

Molecular Formula	C₄₄H₅₁ClN₁₀O₉S
Molecular Weight	931.46

Hazard Codes	Xi

2250025-88-6	24447-13-0
15701-16-3	14265-83-9
149950-61-8	14993-39-6
1421854-16-1	27045-88-1
108173-53-1	337464-42-3
1158522-08-7	940364-43-2
134104-43-1	131615-57-1
6906-52-1	1005878-56-7
930439-75-1	951927-73-4
1018584-77-4	133301-64-1