Table 2. Validation Data for a Selection of Covalent Probes Which Fulfill Quality Criteria.
| Compound | Target | Biochemical potency,kinact/Ki(M–1 s–1) | Cellular potency, IC50 (μM) | Evidence of proteome-wide selectivity | Biophysical proof of target labelingn | Inactive control compound available? |
|---|---|---|---|---|---|---|
| sotorasib28 | KRasG12C | 9,900 | 0.028d | yes | 6OIM(45) | not reported |
| adagrasib27 | KRasG12C | 35,000 | 0.014e | yes | 6USX | not reported |
| osimertinib32,46 | EGFR L858R | 570,00033 | 0.015f | not reported | 6JWL, 6JXO, 6JX4, 6JXT(47) | yes33 |
| VVD-11831341 | JAK1 | not reporteda | 0.032; 0.046g | yes | not provided | not reported |
| compound 3248,49 | JAK3 | 190,000 | 0.331h | yesl | 6DB4m | not reported |
| compound 1942 | PI3Ka | 414,000 | 0.082i | not reported | 7R9V | yes |
| THZ53144,50 | CDK12/13 | not reportedb | j | not reported | 7NXJ(44) | yes, THZ513R |
| roblitinib51 | FGFR4 | not reportedc | 0.0043k | not reported | 6YI8 | not reported |
a
TEC50 = 0.008 μM JAK1_C817.
b
IC50 = 0.158 μM CDK12; IC50 = 0.069 μM CDK13.
c
IC50 = 0.0009 μM FGFR4.
d
pERK in MIA PaCa-2.
e
pERK in NCI-H358.
f
pEGFR in H1975.
g
IFNα-p-STAT1; IL-6-p-STAT1 in hPBMC.
h
IL-15-p-STAT15 in human whole blood.
i
pAKT S473 in SKOV3.
j
Dose-responsive reduction of pSer2 Pol II in Jurkat cells, 50 −500 nM.
k
pFGFR4 in BaF3.
l
For analog, compound 6.
m
For analog, compound 34.
n
PDB code of X-ray cocrystal structure.