Mobocertinib

Mobocertinib
Clinical data
Trade names	Exkivity
Other names	TAK-788, AP-32788
License data	US DailyMed: Mobocertinib;
Pregnancy; category	Contraindicated;
Routes of; administration	By mouth
Drug class	Antineoplastic
ATC code	None;
Legal status
Legal status	US: ℞-only ;
Identifiers
	IUPAC name Propan-2-yl 2-(4-{[2-(dimethylamino)ethyl]methylamino}-2-methoxy-5-(prop-2-enamido)anilino)-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate;
CAS Number	1847461-43-1; as salt: 2389149-74-8;
PubChem CID	118607832;
DrugBank	DB16390; as salt: DBSALT003192;
ChemSpider	84455481;
UNII	39HBQ4A67L; as salt: 53QIA92ZEE;
KEGG	D12001; as salt: D11969;
ChEMBL	ChEMBL4650319;
Chemical and physical data
Formula	C32H39N7O4
Molar mass	585.709 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)OC(=O)C1=CN=C(N=C1C2=CN(C3=CC=CC=C32)C)NC4=C(C=C(C(=C4)NC(=O)C=C)N(C)CCN(C)C)OC;
	InChI InChI=1S/C32H39N7O4/c1-9-29(40)34-24-16-25(28(42-8)17-27(24)38(6)15-14-37(4)5)35-32-33-18-22(31(41)43-20(2)3)30(36-32)23-19-39(7)26-13-11-10-12-21(23)26/h9-13,16-20H,1,14-15H2,2-8H3,(H,34,40)(H,33,35,36); Key:AZSRSNUQCUDCGG-UHFFFAOYSA-N; ; as salt: InChI=1S/C32H39N7O4.C4H6O4/c1-9-29(40)34-24-16-25(28(42-8)17-27(24)38(6)15-14-37(4)5)35-32-33-18-22(31(41)43-20(2)3)30(36-32)23-19-39(7)26-13-11-10-12-21(23)26;5-3(6)1-2-4(7)8/h9-13,16-20H,1,14-15H2,2-8H3,(H,34,40)(H,33,35,36);1-2H2,(H,5,6)(H,7,8); Key:YXYAEUMTJQGKHS-UHFFFAOYSA-N;

Mobocertinib, sold under the brand name Exkivity, is used for the treatment of non-small cell lung cancer.^[2]^[3]

The most common side effects include diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.^[2]

Mobocertinib is a small molecule tyrosine kinase inhibitor. Its molecular target is epidermal growth factor receptor (EGFR) bearing mutations in the exon 20 region.^[4]^[5] Mobocertinib is an irreversible kinase inhibitor, forming a covalent bond with the cysteine 797 in the EGFR active site, leading to sustained inhibition of EGFR enzymatic activity. The irreversible binding leads to increased potency via higher affinity binding, more sustained EGFR kinase activity inhibition, and greater overall selectivity, as only a limited number of other kinases possess a cysteine in the equivalent position.^[6]

Mobocertinib was approved for medical use in the United States in September 2021.^[2]^[3] It is a first-in-class oral treatment to target EGFR Exon20 insertion mutations.^[3]

Medical uses[]

Mobocertinib is indicated for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.^[2]

References[]

^ ^a ^b "Exkivity- mobocertinib capsule". DailyMed. Retrieved 30 September 2021.
^ ^a ^b ^c ^d ^e "FDA grants accelerated approval to mobocertinib for metastatic non-sma". U.S. Food and Drug Administration (FDA). 16 September 2021. Retrieved 16 September 2021. This article incorporates text from this source, which is in the public domain.
^ ^a ^b ^c "Takeda's Exkivity (mobocertinib) Approved by U.S. FDA as the First Oral Therapy Specifically Designed for Patients with EGFR Exon20 Insertion+ NSCLC" (Press release). Takeda Pharmaceutical Company. 15 September 2021. Retrieved 16 September 2021 – via Business Wire.
^ "TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations". Clinicaltrials.gov. 28 January 2021. Retrieved 17 February 2021.
^ Zhang SS, Zhu VW (2021). "Spotlight on Mobocertinib (TAK-788) in NSCLC with EGFR Exon 20 Insertion Mutations". Lung Cancer. 12: 61–65. doi:10.2147/LCTT.S307321. PMC 8286072. PMID 34285620.
^ Gonzalvez F, Vincent S, Baker TE, Gould AE, Li S, Wardwell SD, et al. (July 2021). "Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non-Small Cell Lung Cancer". Cancer Discovery. 11 (7): 1672–1687. doi:10.1158/2159-8290.CD-20-1683. PMID 33632773. S2CID 232056169.

External links[]

"Mobocertinib". Drug Information Portal. U.S. National Library of Medicine.
Clinical trial number NCT02716116 for "A Study of TAK-788 in Adults With Non-Small Cell Lung Cancer" at ClinicalTrials.gov

This antineoplastic or immunomodulatory drug article is a stub. You can help Wikipedia by .

[Exkivity_FDA_label-1] "Exkivity- mobocertinib capsule". DailyMed. Retrieved 30 September 2021.

[FDA_mobocertinib-2] "FDA grants accelerated approval to mobocertinib for metastatic non-sma". U.S. Food and Drug Administration (FDA). 16 September 2021. Retrieved 16 September 2021. This article incorporates text from this source, which is in the public domain.

[Takeda_PR-3] "Takeda's Exkivity (mobocertinib) Approved by U.S. FDA as the First Oral Therapy Specifically Designed for Patients with EGFR Exon20 Insertion+ NSCLC" (Press release). Takeda Pharmaceutical Company. 15 September 2021. Retrieved 16 September 2021 – via Business Wire.

[4] "TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations". Clinicaltrials.gov. 28 January 2021. Retrieved 17 February 2021.

[pmid34285620-5] Zhang SS, Zhu VW (2021). "Spotlight on Mobocertinib (TAK-788) in NSCLC with EGFR Exon 20 Insertion Mutations". Lung Cancer. 12: 61–65. doi:10.2147/LCTT.S307321. PMC 8286072. PMID 34285620.

[6] Gonzalvez F, Vincent S, Baker TE, Gould AE, Li S, Wardwell SD, et al. (July 2021). "Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non-Small Cell Lung Cancer". Cancer Discovery. 11 (7): 1672–1687. doi:10.1158/2159-8290.CD-20-1683. PMID 33632773. S2CID 232056169.

[1]

[2]

[3]

[4]

[5]

[6]