Delving into the Latest Updates on SLB-1122168 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

SPNS2

Mechanism

SPNS2 inhibitors(sphingolipid transporter 2 inhibitors)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesDigestive System Disorders+ [1]

Active Indication

Colitis, UlcerativeMultiple Sclerosis

Inactive Indication-

Originator Organization

Virginia Technologies, Inc.

Active Organization

Virginia Technologies, Inc.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC22H35N3O

InChIKeyOEJNQFOIGSGVNZ-LJQANCHMSA-N

CAS Registry2764877-97-4

Targeting the S1P pathway has resulted in the development of S1P1 receptor modulators for the treatment of multiple sclerosis and ulcerative colitis. We hypothesize that targeting an upstream node of the S1P pathway may provide an improved adverse event profile. In this report, we performed a structure-activity relationship study focusing on the benzoxazole scaffold in SLB1122168, which lead to the discovery of 11i (SLF80821178) as a potent inhibitor of S1P release from HeLa cells (IC₅₀: 51 ± 3 nM). Administration of SLF80821178 to mice induced ∼50% reduction in circulating lymphocyte counts, recapitulating the lymphopenia characteristic of Spns2 null animals. Molecular modeling studies suggest that SLF80821178 binds Spns2 in its occluded inward-facing state and forms hydrogen bonds with Asn112 and Ser211 and π stacking with Phe234. Taken together, SLF80821178 can serve as a scaffold for future inhibitor development and represents a chemical tool to study the therapeutic implication of inhibiting Spns2.

100 Deals associated with SLB-1122168

Login to view more data