Protein Kinase Inhibitors

There are 73 FDA-approved small molecule protein kinase inhibitors as of 7 December 2022 as compiled by Robert Roskoski Jr.

(Deucravacitinib 9 September 2022 | Futibatinib 30 September 2022)

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

1/9

Abemaciclib
4.94/3.76

5/7

2017

CDK4/6

HR+, HER breast Ca

2/6

Abrocitinib
1.25/0.79

3/6

2022

JAK1

Atopic dermatitis

2/6

Acalabrutinib
3.31/2.56

5/4

2017

Bruton tyrosine kinase

Mantle cell lymphoma, CLL, SLL

2/8

Afatinib
4.39/3.76

4/8

2013
2016

EGFR,
ErbB2, ErbB4

NSCLC (2013), squamous NSCLC (2016)

1/5

Alectinib
4.77/4.89

6/3

2015

ALK & RET

ALK+ NSCLC

3/6

Asciminib
3.46/3.86

4/6

2021

Bcr-Abl

Ph+ CML

1/9

Avapritinib
2.61/2.12

6/5

2020

PDGFR

GIST with PDGFR exon 18 mutations

2/4

Axitinib
4.64/4.15

4/5

2012

VEGFR1/2/3, PDGFRβ

RCC

1/7

Baricitinib
1.10/-0.19

4/5

2018

JAK1/2

Rheumatoid arthritis

3/6

Belumosudil
4.82/4.02

5/7

2021

ROCK2

Graft vs. host disease

3/7

Benimetinib
3.01/3.81

3/6

2018

MEK1/2

B-Raf V600E/K melanoma with encorafenib

1/8

Bosutinib
5.19/3.37

4/9

2012

BCR-Abl, Src, Lyn, Hck

CML

2/9

Brigatinib
5.09/2.49

6/8

2017

ALK, ROS1, IGF-1R, Flt3, EGFR

ALK+ NSCLC after
crizotinib

2/7

Cabozantinib
5.54/4.65

4/8

2012
2016

RET, Met, VEGFR1/2/3, Kit,TrkB,
Flt3, Axl, Tie2, ROS1

Metastatic medullary thyroid cancer (2012) and advanced RCC (2016) and HCC (2019)

1/6

Capmatinib
3.43/2.96

5/4

2020

MET

NSCLC with MET exon 14 skipping

3/8

Ceritinib
6.36/3.38

4/9

2014

ALK, IGF-1R, InsR, ROS1

ALK+ NSCLC as first-line treatment or after crizotinib resistance

3/5

Cobimetinib
3.78/2.73

4/4

2015

MEK1/2

Melanoma with BRAF V600E/K mutations with vemurafenib

3/6

Crizotinib
5.04/0.95

4/5

2011

ALK, c-Met (HGFR), ROS1, MST1R

ALK+ NSCLC (2011) and ROS1+ NSCLC (2016)

2/11

Dabrafenib
5.36/5.10

4/6

2013

B-Raf

Melanoma, NSCLC, and anaplastic thyroid cancers with BRAF mutations

2/7

Dacomitinib
5.16/3.53

4/7

2018

EGFR/ErbB2/
ErbB4

EGFR-mutated NSCLC

3/9

Dasatinib
3.31/3.74

4/7

2006

BCR-Abl, EGFR, Src, Lck, Yes, Fyn, Kit, EphA2, PDGFRβ

Ph+ CML or ALL

3/8

Deucravacitinib
1.73/2.39

4/7

2022

TYK2

Psoriasis

3/10

Encorafenib
3.91/2.61

3/10

2018

B-RafV600E/K

B-RafV600E/K mutant melanoma with binimetinib; mutant CRC with cetuximab

3/8

Entrectinib
5.03/4.87

6/7

2019

ROS1+ NSCLC; solid tumors with NTRK fusion proteins

TRKA/B/C, ROS1, ALK

1/7

Erdafitinib
4.18/1.25

4/9

2019

FGFR1/2/3/4

Urothelial (bladder) carcinoma

1/7

Erlotinib
3.41/3.20

3/11

2004

EGFR

NSCLC and pancreatic cancer

3/14

Everolimus
6.20/7.40

3/9

2009

FKBP12/mTOR

HER2 breast cancer, PNET, RCC, RAML, SEGA

3/11

Fedratinib
4.82/3.23

4/11

2019

JAK2

Myelofibrosis

4/14

Fostamatinib
3.09/-0.52

4/10

2018

Syk, Spleen tyrosine kinase

Second-line treatmenet of chronic immune thrombocytopenia

1/7

Futibatinib
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

Gefitinib
4.28/3.64

4/8

2003-2005, 2015

EGFR

NSCLC

3/10

Gilteritinib
2.70/1.69

5/9

2018

FLT3

AML patients with FLT3 mutation5

1/6

Ibrutinib
4.22/3.63

5/5

2013

Bruton tyrosine  kinase

Mantle cell lymphoma,  CLL, Waldenstrom’s macroglobulinemia, graft vs. host disease (2017)

2/7

Imatinib
4.59/3.80

5/7

2001

BCR-Abl, Kit, PDGFR

Ph+ CML or ALL, aggressive systemic mastocytosis, CEL, DFSP, HES, GIST, MDS/MDP

2/8

Infigratinib
5.35/3.99

4/8

2021

FGFRs

Cholangiocarcinomas with FGFR2 fusion proteins

2/9

Lapatinib
6.14/4.40

5/11

2007

EGFR, ErbB2

Breast cancer

2/7

Larotrectinib
2.95/2.44

5/3

2018

NTRK

Solid tumors with NTRK gene fusion proteins

3/5

Lenvatinib
4.07/2.52

4/6

2015

VEGFRs, FGFRs, PDGFR, Kit, RET

DTC

1/7

Lorlatinib
2.80/1.62

3/0

2018

ALK

ALK-positive NSCLC

1/4

Midostaurin
5.91/5.43

8/3

2017

Flt3

Acute myeloid leukemia Flt3 mutation+

2/9

Mobocertinib
5.08/3.79

4/13

2021

EGFR with exon 20 insertions

NSCLC

2/8

Neratinib
5.93/3.05

4/11

2017

ErbB2/HER2

HER2+ breast cancer

2/5

Netarsudil
4.89/3.42

4/8

2018

Rho kinase

Glaucoma

2/9

Nilotinib
6.36/5.35

5/6

2007

BCR-Abl, PDGFR, DDR1

First-line and second-line treatment of Ph+ CML

2/7

Nintedanib
3.62/2.57

5/8

2014

FGFR1/2/3, PDGFRα/β, VEGFR1/2/3, Flt3

Idiopathic pulmonary fibrosis

2/7

Osimertinib
4.51/3.01

4/10

2015

EGFR T970M

NSCLC

1/7

Pacritinib
4.96/3.11

4/4

2022

JAK2

Myelofibrosis

2/8

Palbociclib
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

Pazopanib
3.14/3.55

4/5

2009

VEGFR1/2/3, PDGFRα/β, FGFR1/3, Kit, Lck, Fms, Itk

RCC, soft tissue sarcomas

1/8

Pemigatinib
3.66/1.80

5/6

2020

FGFR2

Cholangiocarcinoma with a FGFR2 fusion or rearrangement

2/7

Pexidartinib
5.23/4.55

4/5

2019

CSFR1/Kit

Tenosynovial giant cell tumors

1/8

Ponatinib
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

Pralsetinib
4.20/3.64

5/8

2020

RET

RET fusion-positive NSCLC; RET mutant medullary thyroid cancer; RET fusion-positive thyroid cancer

3/8

Regorafenib
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

Ribociclib
2.80/0.91

5/5

2017

CDK4/6

HR+-EGFR metastatic breast cancer with an aromatase inhibitor

3/5

Ripretinib
5.67/4.48

5/4

2020

Kit/PDGFRa

Gastrointestinal stromal tumors

1/4

Ruxolitinib
3.47/2.48

4/4

2011

JAK1/2

Myelofibrosis, PV, and atopic dermatitis (September 2021)

1/9

Selpercatinib
3.28/3.11

8/5

2020

RET

RET lung & thyroid cancers

3/6

Selumetinib
3.53/4.27

6/3

2020

MEK1/2

Neurofibromatosis type 1

3/13

Sirolimus
6.18/7.45

3/6

1999

FKBP12/mTOR

Renal transplant, lymphangioleiomyomatosis

3/7

Sorafenib
5.55/4.34

3/5

2005

B/C-Raf, B-Raf (V600E), Kit, Flt3, RET, VEGFR1/2/3, PDGFRβ

Hepatocellular carcinoma, RCC, DTC

3/4

Sunitinib
3.33/1.28

3/7

2006

PDGFRα/β, VEGFR1/2/3, Kit, Flt3, CSF-1R, RET

RCC, GIST, PNET

4/16

Temsirolimus
4.39/?

3/11

2007

FKBP12/mTOR

Advanced RCC

7/7

Tepotinib
4.01/2.26

5/7

2021

Met

Met mutation-positive
NSCLC

2/6

Tivozanib
5.64/4.16

4/6

2021

VEGFR2

Third-line treatment of
RCC

1/5

Tofacitinib
1.54/1.19

3/3

2012

JAK1/3

Rheumatoid arthritis

2/6

Trametinib
3.94/3.18

4/5

2013

MEK1/2

Melanoma (2013) and NSCLC (2017) with BRAF mutations

2/7

Trilaciclib
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

2/8

Tucatinib
5.09/5.25

6/6

2020

ErbB2/HER2

HER2 + breast cancer

2/6

Upadacitinib
2.91/0.85

4/3

2019

JAK1

Rheumatoid arthritis, psoriatic arthritis, atopic dermatitis

1/7

Vandetanib
5.00/2.81

4/6

2011

EGFRs, VEGFRs, RET, Brk, Tie2,
EphRs, Src family kinases

Medullary thyroid cancer

2/7

Vemurafenib
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

2/5

Zanubrutinib
4.22/3.42

5/6

2019

Bruton tyrosine kinase

Mantle cell lymphoma

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 1DFSP, 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) 187, 106552.

See Excel files to download below:
Same information on the 73 FDA-approved drugs for sorting
Additional information on the 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