JH-XI-10-02

JH-XI-10-02 is a highly potent and selective PROTAC CDK8 degrader, with an IC50 of 159 nM. JH-XI-10-02 causes proteasomal degradation, does not affect CDK8 mRNA levels. JH-XI-10-02 shows no effect on CDK19.

Product information

CAS Number: 2209085-22-1

Molecular Weight: 920.14

Formula: C53H69N5O9

Chemical Name: N-[(1S,3aS,3bR,5aS,7S,9aS,9bS,11aS)-3a,3b,5a,9b-tetrahydrogenio-1-(isoquinolin-7-yl)-9a,11a-dimethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-7-yl]-1-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]amino}-N-methyl-3,6,9,12-tetraoxapentadecan-15-amide

Smiles: CN([C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@H](C5=CC6C=NC=CC=6C=C5)[C@@]4(C)CC[C@@H]3[C@@]2(C)CC1)C(=O)CCOCCOCCOCCOCCNC1=CC=CC2=C1C(=O)N(C1CCC(=O)NC1=O)C2=O

InChiKey: JECHBTRAPARMGI-GFTKVEOVSA-N

InChi: InChI=1S/C53H69N5O9/c1-52-19-15-38(32-37(52)9-10-39-42-12-11-41(53(42,2)20-16-43(39)52)35-8-7-34-17-21-54-33-36(34)31-35)57(3)47(60)18-23-64-25-27-66-29-30-67-28-26-65-24-22-55-44-6-4-5-40-48(44)51(63)58(50(40)62)45-13-14-46(59)56-49(45)61/h4-8,17,21,31,33,37-39,41-43,45,55H,9-16,18-20,22-30,32H2,1-3H3,(H,56,59,61)/t37-,38-,39-,41+,42-,43-,45?,52-,53+/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 100 mg/mL (108.68 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

JH-XI-10-02, a bivalent small molecule degrader, recruits the E3 ligase CRL4Cereblon to promote the ubiquitination and proteosomal degradation of CDK8. JH-XI-10-02 (1 μM) induces partial degradation of CDK8 in Jurkat cells upon treatment for 6 h. JH-XI-10-02 (1 μM) induces significant degradation of CDK8 after treatment for 24 h. JH-XI-10-02 induces degradation of CDK8 at 5 μM in WT Molt4 cells, no degradation in CRBN null Molt4 cells at any concentration (0.1-5 μM) in WT Molt4 cells and Molt4 cells where CRBN had been subject to CRISPER/CAS9-mediated deletion for 24 h.

Products are for research use only. Not for human use.