Dacomitinib

Dacomitinib
Names

IUPAC name (2E)-N-{4-[(3-Chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolinyl}-4-(1-piperidinyl)-2-butenamide
Other names PF-00299804
Identifiers
CAS Number	1110813-31-4^Y
3D model (Jmol)	Interactive image
ChEBI	CHEBI:132268
ChEMBL	ChEMBL2105719
ChemSpider	9685914
IUPHAR/BPS	7422
PubChem	11511120
UNII	2XJX250C20^Y
InChI InChI=1S/C24H25ClFN5O2/c1-33-22-14-20-17(24(28-15-27-20)29-16-7-8-19(26)18(25)12-16)13-21(22)30-23(32)6-5-11-31-9-3-2-4-10-31/h5-8,12-15H,2-4,9-11H2,1H3,(H,30,32)(H,27,28,29)/b6-5+ Key: LVXJQMNHJWSHET-AATRIKPKSA-N InChI=1/C24H25ClFN5O2/c1-33-22-14-20-17(24(28-15-27-20)29-16-7-8-19(26)18(25)12-16)13-21(22)30-23(32)6-5-11-31-9-3-2-4-10-31/h5-8,12-15H,2-4,9-11H2,1H3,(H,30,32)(H,27,28,29)/b6-5+ Key: LVXJQMNHJWSHET-AATRIKPKBC
SMILES COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)/C=C/CN4CCCCC4
Properties
Chemical formula	C₂₄H₂₅ClFN₅O₂
Molar mass	469.95 g·mol⁻¹
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Dacomitinib (PF-00299804) is an experimental drug candidate under development by Pfizer for the treatment of non-small-cell lung carcinoma. It is a selective and irreversible inhibitor of EGFR.^[1]

Dacomitinib has advanced to several Phase III clinical trials. The results of the first trials were disappointing, with a failure to meet the study goals,^[2]^[3]^[4] Additional Phase III trials are ongoing.^[2]

References

↑ "Dacomitinib". NCI Drug Dictionary.
1 2 Zosia Chustecka (January 27, 2014). "Dacomitinib Fails in Pretreated Non-small Cell Lung Cancer". Medscape.
↑ "Blow to Pfizer as dacomitinib fails in lung cancer trials". pmlive.com. 28 January 2014.
↑ "Pfizer Announces Top-Line Results From Two Phase 3 Trials Of Dacomitinib In Patients With Refractory Advanced Non-Small Cell Lung Cancer". Pfizer Press Release. January 27, 2014.

External links

Dacomitinib Fact Sheet, Pfizer

Growth factor receptor modulators

Angiopoietin

Agonists: Angiopoietin 1
Angiopoietin 4

Antagonists: Angiopoietin 2
Angiopoietin 3

Antibodies: Evinacumab (against angiopoietin 3)
Nesvacumab (against angiopoietin 2)

CNTF

Agonists: Axokine
CNTF
Dapiclermin

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists: Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Antibodies: Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab Kinase inhibitors: Afatinib AG-490 Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154

ErbB2/HER2	Agonists: Unknown/none Antibodies: Ertumaxomab Pertuzumab Trastuzumab Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors: Afatinib AG-490 Lapatinib Mubritinib Neratinib

ErbB3/HER3	Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C)) Antibodies: Duligotumab Patritumab Seribantumab

ErbB4/HER4	Agonists: Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))

FGF

FGFR1	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20) Repifermin Trafermin Velafermin

FGFR2	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22) Palifermin Repifermin Sprifermin Trafermin Antibodies: Aprutumab Aprutumab ixadotin

FGFR3	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 8, 9, 18, 23) Sprifermin Trafermin Antibodies: Burosumab (against FGF23)

FGFR4	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 6, 8, 9, 19) Trafermin

Unsorted	Agonists: FGF15/19

HGF (c-Met)

Agonists: Hepatocyte growth factor

Potentiators: Dihexa (PNB-0408)

Antibodies: Emibetuzumab
Ficlatuzumab
Flanvotumab
Onartuzumab
Rilotumumab
Telisotuzumab
Telisotuzumab vedotin

Kinase inhibitors: AM7 (drug)
AMG-458
Amuvatinib
BMS-777607
Cabozantinib
Crizotinib
Foretinib
Golvatinib
INCB28060
JNJ-38877605
K252a
MK-2461
PF-04217903
PF-2341066
PHA-665752
SU-11274
Tivantinib
Volitinib

IGF

IGF-1	Agonists: des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Antagonists: BMS-754807 Antibodies: AVE1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Kinase inhibitors: Linsitinib NVP-ADW742 NVP-AEW541 OSl-906

IGF-2	Agonists: Insulin-like growth factor-2 (somatomedin A) Antibodies: Dusigitumab

Others	Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7) Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) Trofinetide

LNGF

Agonists: BDNF
Cenegermin
NGF
NT-3
NT-4

Antagonists: SAR127963

Antibodies: Against NGF: Fasinumab
Fulranumab
Ranevetmab
Tanezumab

PDGF

Agonists: Becaplermin
Platelet-derived growth factor (A, B, C, D)

RET (GFL)

GFRα1	Agonists: Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors: Vandetanib

GFRα2	Agonists: Neurturin (NRTN) Kinase inhibitors: Vandetanib

GFRα3	Agonists: Artemin (ARTN) Kinase inhibitors: Vandetanib

GFRα4	Agonists: Persephin (PSPN) Kinase inhibitors: Vandetanib

Unsorted	Kinase inhibitors: Agerafenib

SCF (c-Kit)

Agonists: Ancestim
Stem cell factor

TGFβ

See here instead.

Trk

TrkA	Agonists: Amitriptyline Cenegermin Gambogic amide NGF Tavilermide Antagonists: FX007 Kinase inhibitors: Entrectinib K252a Lestaurtinib LOXO-101 Antibodies: Against NGF: Fasinumab Fulranumab Ranevetmab Tanezumab

TrkB	Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF Deoxygedunin Diosmetin HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 TDP6 Antagonists: ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Kinase inhibitors: Entrectinib K252a Lestaurtinib LOXO-101

TrkC	Agonists: NT-3 Kinase inhibitors: Entrectinib K252a Lestaurtinib LOXO-101

VEGF

Agonists: Placental growth factor (PGF)
Telbermin
VEGF (A, B, C, D (FIGF))

Allosteric modulators: Cyclotraxin B

Decoy receptors: Aflibercept

Others

Additional growth factors: Adrenomedullin
Colony-stimulating factors (see here instead)
Connective tissue growth factor (CTGF)
Ephrins (A1, A2, A3, A4, A5, B1, B2, B3)
Erythropoietin (see here instead)
Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
Glia maturation factor (GMF)
Hepatoma-derived growth factor (HDGF)
Interleukins/T-cell growth factors (see here instead)
Leukemia inhibitory factor (LIF)
Macrophage-stimulating protein (MSP; HLP, HGFLP)
Midkine (NEGF2)
Migration-stimulating factor (MSF; PRG4)
Oncomodulin
Pituitary adenylate cyclase-activating peptide (PACAP)
Pleiotrophin
Renalase
Thrombopoietin (see here instead)
Wnt signaling proteins

Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)

See also: Peptide receptor modulators
Cytokine receptor modulators

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