23 March 2020

Fragments in the clinic: 2020 edition

As I write this, more than 350,000 people worldwide have tested positive for SARS-CoV-2. More than 15,000 of them have died.

It is important to stay aware of what's going on and take appropriate measures to stop the spread of COVID-19. But to paraphrase Nietzsche, one can spend too much time staring into the abyss. In the spirit of hope, Practical Fragments offers an updated list of FBLD-derived drugs.

The current list contains 47 molecules, 7 more than the last compilation, with 4 approved. 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 list contains a higher proportion of compounds that are no longer progressing. 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. The list is almost certainly incomplete, particularly for Phase 1 compounds. If you know of any others (and can mention them) please leave a comment.

DrugCompanyTarget
Approved!

ErdafitinibAstex/J&JFGFR1-4
PexidartinibPlexxikonCSF1R, KIT
VemurafenibPlexxikonB-RAFV600E
VenetoclaxAbbVie/GenentechSelective BCL-2
Phase 3

AsciminibNovartisBCR-ABL
LanabecestatAstex/AstraZeneca/LillyBACE1
VerubecestatMerckBACE1
Phase 2

AMG 510Amgen KRASG12C
ASTX660AstexXIAP/cIAP1
AT7519AstexCDK1,2,4,5,9
AT9283 AstexAurora, JAK2
AUY-922Vernalis/NovartisHSP90
AZD5363AstraZeneca/Astex/CR-UKAKT
AZD5991AstraZenecaMCL1
CPI-0610ConstellationBET
DG-051deCODELTA4H
eFT508eFFECTORMNK1/2
IndeglitazarPlexxikonpan-PPAR agonist
LY2886721LillyBACE1
LY3202626LillyBACE1
LY517717Lilly/ProthericsFXa
MAK683NovartisPRC2 EED
Navitoclax (ABT-263)AbbottBCL-2/BCLxL
OnalespibAstexHSP90
PF-06650833PfizerIRAK4
PF-06835919PfizerKHK
Phase 1

ABBV-744AbbottBD2-selective BET
ABT-518AbbottMMP-2 & 9
ABT-737AbbottBCL-2/BCLxL
ASTX029AstexERK1,2
AT13148AstexAKT, p70S6K, ROCK
AZD3839AstraZenecaBACE1
AZD5099AstraZenecaBacterial topoisomerase II
BI 691751Boehringer IngelheimLTA4H
ETC-206D3MNK1/2
GDC-0994Genentech/ArrayERK2
HTL0014242Sosei HeptaresmGlu5 NAM
IC-776Lilly/ICOSLFA-1
LP-261LocusTubulin
LY2811376LillyBACE1
MivebresibAbbVieBRD2-4
NavoximodNew Link/GenentechIDO1
PLX5568PlexxikonRAF
S64315Vernalis/Servier/NovartisMCL1
SGX-393SGXBCR-ABL
SGX-523SGXMET
SNS-314SunesisAurora

We live in scary times. But, as this list demonstrates, by working together we can still achieve marvels.

5 comments:

Troy said...

Phase 1/2A clinical trial of VK-2019 (that targets EBNA1) in patients with EBV-positive advanced nasopharyngeal carcinoma. (https://clinicaltrials.gov/ct2/show/NCT03682055). Molecule was discovered and developed by the Wistar Institute and licensed by Cullinan Oncology. (https://www.cullinanoncology.com/2019/01/30/cullinan-to-develop-ebna1-inhibitor/)

Dan Erlanson said...

Hi Troy,

Congratulations - is this related to your work that we profiled here?

And via LinkedIn, Alastair Donald noted that AZD5363 (capivasertib) is actually already in Phase 3.

So out of date in less than a day - in a good way!

Unknown said...

I am surprised that you list Verubecestat and Lanabecestat, both BACE1 inhibitors.
As far as I know the plug has been pulled on them due to inefficacy, or even
making things worse.

Unknown said...

Also, LY2811376 has been dropped.

Dan Erlanson said...

Thanks Unknown. As I write above, "As always, this table includes compounds whether or not they are still in development..."