21 November 2022

Fragments in the clinic: 2022 edition

In the US we're about to celebrate Thanksgiving. One of the things I'm thankful for is the discovery of new medicines, so this seems like an appropriate time to update our tally of fragment-derived drugs.
 
As always, this table includes compounds whether or not they are still in development (indeed, some of the companies no longer even exist). Because of this, the Phase 1 section contains a higher proportion of compounds that are no longer progressing. The full list contains 58 molecules, up from 52 last year, with more than 40% approved or in active trials: not bad given that only about 10% of drugs that make it into the clinic are ultimately approved.
 
Drugs reported as still active in clinicaltrials.gov, company websites, or other sources are in bold, and the 36 that have been discussed on Practical Fragments are hyperlinked to the most relevant post. The list is almost certainly incomplete, particularly for Phase 1 compounds. If you know of others please leave a comment.

DrugCompanyTarget
Approved!

AsciminibNovartisBCR-ABL1
ErdafitinibAstex/J&JFGFR1-4
PexidartinibPlexxikonCSF1R, KIT
Sotorasib
Amgen KRASG12C
VemurafenibPlexxikonB-RAFV600E
VenetoclaxAbbVie/GenentechSelective BCL-2
Phase 3

Capivasertib
AstraZeneca/Astex/CR-UKAKT
LanabecestatAstex/AstraZeneca/LillyBACE1
Navitoclax (ABT-263)AbbottBCL-2/BCLxL
Pelabresib (CP-0610)
ConstellationBET
VerubecestatMerckBACE1
Phase 2

ASTX029AstexERK1,2
ASTX660AstexXIAP/cIAP1
AT7519AstexCDK1,2,4,5,9
AT9283 AstexAurora, JAK2
AUY-922Vernalis/NovartisHSP90
AZD5991AstraZenecaMCL1
DG-051deCODELTA4H
eFT508eFFECTORMNK1/2
IndeglitazarPlexxikonpan-PPAR agonist
LY2886721LillyBACE1
LY3202626LillyBACE1
LY3372689LillyOGA
LY517717Lilly/ProthericsFXa
LYS006Novartis
LTA4H
MAK683NovartisPRC2 EED
OnalespibAstexHSP90
PF-06650833PfizerIRAK4
PF-06835919PfizerKHK
PLX51107PlexxikonBET
S64315Vernalis/Servier/NovartisMCL1
VK-2019
Cullinan Oncology / Wistar
EBNA1
Phase 1

AG-270
Agios/Servier
MAT2A
ABBV-744AbbottBD2-selective BET
ABT-518AbbottMMP-2 & 9
ABT-737AbbottBCL-2/BCLxL
AT13148AstexAKT, p70S6K, ROCK
AZD3839AstraZenecaBACE1
AZD5099AstraZenecaBacterial topoisomerase II
BI 1823911Boehringer IngelheimKRASG12C
BI 691751Boehringer IngelheimLTA4H
CFTX-1554Confo TherapeuticsAT2 receptor
ETC-206D3MNK1/2
GDC-0994Genentech/ArrayERK2
HTL0014242Sosei HeptaresmGlu5 NAM
HTL0018318Sosei HeptaresM1-receptor partial agonist
HTL9936Sosei HeptaresM1-receptor partial agonist
IC-776Lilly/ICOSLFA-1
LP-261LocusTubulin
LY2811376LillyBACE1
MivebresibAbbVieBRD2-4
MRTX1719MiratiPRMT5•MTA
NavoximodNew Link/GenentechIDO1
PLX5568PlexxikonRAF
SGX-393SGXBCR-ABL
SGX-523SGXMET
SNS-314SunesisAurora
TAK-020
Takeda
BTK


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