Protein Kinase Inhibitors
From the Blue Ridge Institute for Medical Research in Horse Shoe, North Carolina USA
There are 77 FDA-approved small molecule protein kinase inhibitors as of 19 September 2023 as compiled by Robert Roskoski Jr.
(Pirtobrutinib, 23 February 2023 | Ritlecitinib, 28 June 2023 | Quizartinib, 20 July 2023) | Momelotinib, 15 September 2023)
To download an Excel file with the same information that can be used for sorting, click here.
For additional information on the FDA-approved small molecule inhibitors, click here.
The figures are drawn is such a fashion that the left-most portion of the drug extends toward or into the solvent, and the right side of the molecule interacts with hinge residues and hydrophobic components of target protein kinases, except for everolimus, sirolimus, and temsirolimus which bind to FKBP12 and indirectly inhibit mTOR. All drugs are effective orally, except for temsirolimus and trilaciclib, which are given intravenously, and netarsudil, an eye-drop.
Click on the images to view a larger version.
Structurea, name, trade name, company, formula, molecular wt
D/Ab
Drug
ALogPc: cLogDd
Rings/
Rotatable bonds
Yeare
Known Targets
Indicationsf
FDA Label
2/7
5.54/4.65
4/8
2016
RET, Met, VEGFR1/2/3, Kit,TrkB,
Flt3, Axl, Tie2, ROS1
Metastatic medullary thyroid cancer (2012) and advanced RCC (2016) and HCC (2019)
3/8
6.36/3.38
4/9
2014
ALK, IGF-1R, InsR, ROS1
ALK+ NSCLC as first-line treatment or after crizotinib resistance
3/6
5.04/0.95
4/5
2011
ALK, c-Met (HGFR), ROS1, MST1R
ALK+ NSCLC (2011) and ROS1+ NSCLC (2016)
2/11
5.36/5.10
4/6
2013
B-Raf
Melanoma, NSCLC, and anaplastic thyroid cancers with BRAF mutations
3/9
3.31/3.74
4/7
2006
BCR-Abl, EGFR, Src, Lck, Yes, Fyn, Kit, EphA2, PDGFRβ
Ph+ CML or ALL
3/10
3.91/2.61
3/10
2018
B-RafV600E/K
B-RafV600E/K mutant melanoma with binimetinib; mutant CRC with cetuximab
3/8
5.03/4.87
6/7
2019
ROS1+ NSCLC; solid tumors with NTRK fusion proteins
TRKA/B/C, ROS1, ALK
4/14
3.09/-0.52
4/10
2018
Syk, Spleen tyrosine kinase
Second-line treatmenet of chronic immune thrombocytopenia
1/7
1.78/1.54
4/6
2022
FGFR2
Cholangiocarcinomas with FGFR2 fusions or other rearrangements
Approval withdrawn in the USA, but it is approved in dozens of countries. US FDA approval reinstated 15 July 2015.
1/8
4.28/3.64
4/8
2003-2005, 2015
EGFR
NSCLC
1/6
4.22/3.63
5/5
2013
Bruton tyrosine kinase
Mantle cell lymphoma, CLL, Waldenstrom’s macroglobulinemia, graft vs. host disease (2017)
2/7
4.59/3.80
5/7
2001
BCR-Abl, Kit, PDGFR
Ph+ CML or ALL, aggressive systemic mastocytosis, CEL, DFSP, HES, GIST, MDS/MDP
2/9
6.36/5.35
5/6
2007
BCR-Abl, PDGFR, DDR1
First-line and second-line treatment of Ph+ CML
2/7
3.62/2.57
5/8
2014
FGFR1/2/3, PDGFRα/β, VEGFR1/2/3, Flt3
Idiopathic pulmonary fibrosis
2/8
2.97/1.30
5/5
2015
CDK4/6
ER+ and HER2 breast cancer as first-line (2015) and second-line therapy (2016)
2/8
3.14/3.55
4/5
2009
VEGFR1/2/3, PDGFRα/β, FGFR1/3, Kit, Lck, Fms, Itk
RCC, soft tissue sarcomas
1/8
4.66/4.54
5/6
2012
BCR-Abl, BCR-Abl T315I, VEGFR, PDGFR, FGFR, EphR, Src family kinases, Kit, RET, Tie2, Flt3
Ph+ CML or ALL
3/9
4.20/3.64
5/8
2020
RET
RET fusion-positive NSCLC; RET mutant medullary thyroid cancer; RET fusion-positive thyroid cancer
3/8
5.69/4.49
3/5
2012
VEGFR1/2/3, BCR-Abl, B-Raf, B-Raf(V600E), Kit, PDGFRα/β, RET, FGFR1/2, Tie2, Eph2A
CRC, GIST
2/7
2.80/0.91
5/5
2017
CDK4/6
HR+-EGFR metastatic breast cancer with an aromatase inhibitor
1/4
3.47/2.48
4/4
2011
JAK1/2
Myelofibrosis, PV, and atopic dermatitis (September 2021)
3/7
5.55/4.34
3/5
2005
B/C-Raf, B-Raf (V600E), Kit, Flt3, RET, VEGFR1/2/3, PDGFRβ
Hepatocellular carcinoma, RCC, DTC
2/7
2.72/2.29
6/3
2021
CDK4/6
Chemotherapy-induced myelosuppression when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer
2/6
2.91/0.85
4/3
2019
JAK1
Rheumatoid arthritis, psoriatic arthritis, atopic dermatitis
1/7
5.00/2.81
4/6
2011
EGFRs, VEGFRs, RET, Brk, Tie2,
EphRs, Src family kinases
Medullary thyroid cancer
2/7
5.54/4.61
4/7
2011
A/B/C-Raf, B-Raf (V600E), SRMS, ACK1, MAP4K5, FGR
Melanoma with BRAFV600E mutation and Erdheim-Chester disease
aStructures drawn with Accelrys Draw 4.1, Accelrys, Inc. San Diego, CA 92121.
bD, number of hydrogen bond donors; A, number of hydrogen bond acceptors.
cAtom-based calculated log of the partition coefficient; dCalculated log of the distribution coefficient at pH 7.4. Values for ALogP and cLogD from https://www.ebi.ac.uk/chembl/. The partition coefficient (P) is the solubility where pH is not taken into account. The distribution coefficient (D) is the ratio of a compounds solubility in n-octanol/water at pH 7.4.
eYear approved
fALL, acute lymphoblastic leukemia, CEL, chronic eosinophilic leukemia; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CRC, colorectal cancer; DDR1, Discoidin domain receptor family, member 1; DFSP, dermatofibrosarcoma protuberans; DTC, differentiated thyroid carcinoma; GIST, gastrointestinal stromal tumor;
HER2, HER2 negative; HES, hypereosinophilic syndrome, HGFR, hepatocyte growth factor recepter; MDS/MPD, myelodisplastic/myeloproliferative diseases; MST1R, macrophage-stimulating protein receptor aka RON (Recepteur d’Origine Nantais); NSCLC, non-small cell lung cancer; PNET, progressive neuroendocrine tumors of pancreatic origin; Ph+, Philadelphia chromosome positive; PV, polycythemia vera; RAML, renal angiomyolipoma; RCC, renal cell carcinoma; SEGA, subependymal giant cell astrocytoma; SLL small lymphocytic lymphoma. See the drug label for specifics. For example, one indication for everolimus is for postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole. Ponatinib, Regorafenib, Ruxolitinib, Sirolimus, Sorafenib, Sunitinib, Temsirolimus
For reviews of the the first 62 US FDA-approved drugs see the following three papers:
Properties of FDA-approved small molecule protein kinase inhibitors. Pharmacol Res. (2019) 144, 19-50,
Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update. Pharmacol Res. (2020) 152, 104609,
Properties of FDA-approved small molecule protein kinase inhibitors: A 2022 update. Pharmacol Res. (2022) 175, 106037, and
Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update. Pharmacol. Res. (2023) 106552. The latest update did not include deucravacitinib or pirtoburtinib.
See Excel files to download below:
Same information on the 77 FDA-approved drugs for sorting
Additional information on the 77 FDA-approved small molecule inhibitors
The advantage of the spreadsheet format is that one can sort by molecular weight, year approved, number of hydrogen-bond donors, etc.
List of all protein kinase inhibitors in clinical trials.
To report updates or errors, please email
Posted 9 December 2012. Updated 26 July 2023.