05 January 2015

Fragments in the clinic: 2015 edition

It’s been two years since Practical Fragments updated its list of fragment-derived compounds in the clinic, and since then there have been some nice developments. The table below starts from the previous list and also includes everything new we've managed to find. As before, this includes compounds whether or not they are still in development (indeed, some of the companies no longer even exist). Drugs reported as still active in clinicaltrials.gov, company websites, or other sources are in bold, and those that have been discussed on Practical Fragments are hyperlinked to the most relevant post.

Drug Company Target

Vemurafenib (PLX4032) Plexxikon B-Raf(V600E) inhibitor
Phase 3

ABT-199 Abbott Selective Bcl-2 inhibitor
LEE011 Novartis/Astex CDK4 inhibitor
MK-8931 Merck BACE1 inhibitor
Phase 2

AT13387 Astex HSP90 inhibitor
AT7519 Astex CDK1,2,4,5 inhibitor
AT9283  Astex Aurora, Janus kinase 2 inhibitor
AUY922 Vernalis/Novartis HSP90 inhibitor
AZD3293 AstraZeneca/Astex/Lilly BACE1 inhibitor
AZD5363 AstraZeneca/Astex/CR-UK AKT inhibitor
Indeglitazar Plexxikon pan-PPAR agonist
Linifanib (ABT-869) Abbott VEGF & PDGFR inhibitor
LY2886721 Lilly BACE1 inhibitor
LY517717 Lilly/Protherics FXa inhibitor
Navitoclax (ABT-263) Abbott Bcl-2/Bcl-xL inhibitor
PLX3397 Plexxikon FMS, KIT, and FLT-3-ITD inhibitor
Phase 1

ABT-518AbbottMMP-2 & 9 inhibitor
ABT-737AbbottBcl-2/Bcl-xL inhibitor
AT13148AstexAKT, p70S6K inhibitor
AZD3839AstraZenecaBACE1 inhibitor
AZD5099AstraZenecaBacterial topoisomerase II inhibitor
DG-051deCODELTA4H inhibitor
IC-776Lilly/ICOSLFA-1 inhibitor
JNJ-42756493J&J/AstexFGFr inhibitor
LP-261LocusTubulin binder
LY2811376LillyBACE1 inhibitor
PLX5568Plexxikonkinase inhibitor
(RG-7129)RocheBACE1 inhibitor
SGX-393SGXBcr-Abl inhibitor
SGX-523SGXMet inhibitor
SNS-314SunesisAurora inhibitor
UndisclosedVernalis/ServierBcl-2 inhibitor

The current list contains more than 30 clinical-stage drugs but is certainly incomplete, particularly in Phase I. If you know of any others (and can mention them) please leave a comment.


BiotechDueDiligence said...

As a reminder, AStex was acquired by Otsuka, so updates may be less frequent but may show up here:

Also, Novartis recently returned rights to AUY922 to Vernalis, placing its future highly in doubt given the shift in corporate strategy by Vernalis.

DatamonitorMark said...

Navitoclax should be de-bolded. It was halted due to dose-dependent thrombocytopenia. Its successor is ABT-199 (venetoclax), which also had a rocky time a couple of years ago when deaths due to tumor lysis syndrome triggered a clinical hold, but that problem seems to have been surmounted.

Dan Erlanson said...

Just a few updates: PLX3397 is now in Phase 3, and Vernalis has an open phase 2 trial for their FAAH inhibitor V158866.

Dan Erlanson said...

Another update: ABL001, an allosteric Abl inhibitor from Novartis, is in a Phase 1 trial for CML and ALL - stay tuned for more details!

Dan Erlanson said...

Fresh from Pacifichem, ASTX660, Astex's cIAP/XIAP inhibitor, is now in a Phase 1-2 trial for advanced solid tumors and lymphomas.