SJFα, potent and selective p38α PROTAC

SJFα is a novel isoform-selective PROTAC p38α degrader. SJFα comprises the multikinase inhibitor foretinib joined by a linker to a VHL ligand. Displays significantly lower potency degradation at p38δ (DC50 = 299 nM). Exhibits no significant degradation of p38β or γ. or related MAPKs, ERK1/2, or JNK1/2.

Product information

CAS Number: 2254609-27-1

Molecular Weight: 1120.27

Formula: C59H67F2N7O11S

Synonym:

SJFα

SJF α

SJF-α

Chemical Name: N-(3-Fluoro-4-((7-(4-(4-(2-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-2-oxoethoxy)butoxy)butoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Smiles: CC(C)(C)[C@H](NC(=O)COCCCCOCCCCOC1=CC2=NC=CC(OC3=CC=C(C=C3F)N(C(=O)C3(CC3)C(N)=O)C3C=CC(F)=CC=3)=C2C=C1OC)C(=O)N1C[C@H](O)C[C@H]1C(=O)NCC1C=CC(=CC=1)C1SC=NC=1C

InChiKey: CGOWEGDPCPSDKZ-WFYKIECOSA-N

InChi: InChI=1S/C59H67F2N7O11S/c1-36-52(80-35-65-36)38-12-10-37(11-13-38)32-64-54(71)46-29-42(69)33-67(46)55(72)53(58(2,3)4)66-51(70)34-77-26-7-6-24-76-25-8-9-27-78-50-31-45-43(30-49(50)75-5)47(20-23-63-45)79-48-19-18-41(28-44(48)61)68(40-16-14-39(60)15-17-40)57(74)59(21-22-59)56(62)73/h10-20,23,28,30-31,35,42,46,53,69H,6-9,21-22,24-27,29,32-34H2,1-5H3,(H2,62,73)(H,64,71)(H,66,70)/t42-,46+,53-/m1/s1

Technical Data

Appearance: Solid powder

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

Solubility: Soluble in DMSO

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

References:

1. Smith et al (2019) Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase. Nat. Commun. 10, 131.

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