Mobocertinib

Mobocertinib
Clinical data
Trade namesExkivity
Other namesTAK-788, AP-32788
License data
Pregnancy
category
Routes of
administration		By mouth
Drug classAntineoplastic
ATC code
Legal status
Legal status
Identifiers
  • 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
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC32H39N7O4
Molar mass585.709 g·mol−1
3D model (JSmol)
  • 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=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.[6][8]

The most common side effects include diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.[6]

Mobocertinib is a small molecule tyrosine kinase inhibitor structurally similar to osimertinib (differs only by the presence of an additional isopropyl ester group).[9] Its molecular target is epidermal growth factor receptor (EGFR) bearing mutations in the exon 20 region.[10][11] 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.[12]

Mobocertinib was approved for medical use in the United States in September 2021.[6][8] It is a first-in-class oral treatment to target EGFR Exon20 insertion mutations.[8]

  1. ^ a b "Exkivity APMDS". Therapeutic Goods Administration (TGA). 1 August 2022. Archived from the original on 2 August 2022. Retrieved 2 August 2022.
  2. ^ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 21 December 2022. Archived from the original on 3 April 2022. Retrieved 2 January 2023.
  3. ^ a b "Exkivity- mobocertinib capsule". DailyMed. U.S. National Library of Medicine. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  4. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  5. ^ "Exkivity 40 mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 24 March 2022. Archived from the original on 25 March 2022. Retrieved 24 March 2022.
  6. ^ a b c d "FDA grants accelerated approval to mobocertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations". U.S. Food and Drug Administration (FDA). 16 September 2021. Archived from the original on 16 September 2021. Retrieved 16 September 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  7. ^ "Takedas Exkivity mobocertinib Receives Approval from the NMPA of China Becoming the First and Only Therapy Available for Patients with EGFR Exon20 Insertion+ NSCLC" (Press release). Takeda. 11 January 2023. Archived from the original on 10 February 2023. Retrieved 10 February 2023.
  8. ^ 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. Archived from the original on 17 September 2021. Retrieved 16 September 2021 – via Business Wire.
  9. ^ Wang J, Lam D, Yang J, Hu L (October 2022). "Discovery of mobocertinib, a new irreversible tyrosine kinase inhibitor indicated for the treatment of non-small-cell lung cancer harboring EGFR exon 20 insertion mutations". Medicinal Chemistry Research. 31 (10): 1647–1662. doi:10.1007/s00044-022-02952-5. PMC 9433531. PMID 36065226.
  10. ^ "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. Archived from the original on 2 August 2022. Retrieved 17 February 2021.
  11. ^ Zhang SS, Zhu VW (2021). "Spotlight on Mobocertinib (TAK-788) in NSCLC with EGFR Exon 20 Insertion Mutations". Lung Cancer: Targets and Therapy. 12: 61–65. doi:10.2147/LCTT.S307321. PMC 8286072. PMID 34285620.
  12. ^ 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.