Nemtabrutinib

Nemtabrutinib

Clinical data
Other names	MK-1026; ARQ 531
Legal status
Legal status	Investigational
Identifiers
CAS Number	2095393-15-8
PubChem CID	129045720
UNII	JTZ51LIXN4
Chemical and physical data
Formula	C25H23ClN4O4
Molar mass	478.93 g·mol−1

Nemtabrutinib (MK-1026, formerly ARQ 531) is a small molecule drug is a Bruton's tyrosine kinase (BTK) inhibitor; unlike first generation BTK inhibitors it does not bind covalently|Covalent bond]], and inhibits the ATP binding site of BTK, and was designed to inhibit Src family kinases and kinases related to ERK signalling, along with BTK. ^[1]

Merck paid $2.7 billion to acquire the company ArQule and the drug, which at the time had just completed a Phase I clinical trial as a treatment for B-cell cancers. ^[2] As of December 2024 Merck had started Phase III trials in chronic lymphocytic leukaemia and other blood cancers, and had finished a Phase I trial for kidney disease. ^{[3] [4]}

References

1. Shirley, M (January 2022). "Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies: Their Use and Differential Features". Targeted oncology. 17 (1): 69–84. doi:10.1007/s11523-021-00857-8. PMC   8783859 . PMID   34905129.
2. Lisa m. Jarvis (16 December 2019). "Merck will pay $2.7 billion for ArQule" . C&EN Global Enterprise. 97 (48): 13. doi:10.1021/cen-09748-buscon4. ISSN   2474-7408. S2CID   212811804.
3. Hays, Priya (14 June 2025). "Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia". Discover Oncology. 16 (1). doi:10.1007/s12672-025-02947-9. PMC   12167177 . PMID   40515863.
4. "Nemtabrutinib - Merck - AdisInsight". adisinsight.springer.com. Retrieved 13 July 2025.

Further reading

• Sevindik, Ömür Gökmen; Chen, Chang; Yang, Jing; Farooqui, Mohammed Z.H.; Paszkiewicz-Kozik, Ewa (1 June 2023). "BELLWAVE-008: A phase 3 study of the efficacy and safety of nemtabrutinib in previously untreated patients (pts) with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without TP53 aberrations". Journal of Clinical Oncology. 41 (16_suppl): TPS7594. doi:10.1200/JCO.2023.41.16_suppl.TPS7594. S2CID   259080098.
• Woyach, J.; Flinn, I. W.; Awan, F. T.; Eradat, H.; Brander, D.; Tees, M.; Parikh, S. A.; Phillips, T.; Wang, W.; Reddy, N. M.; Farooqui, M. Z.; Byrd, J. C.; Stephens, D. M. (23 June 2022). "P682: Nemtabrutinib (Mk-1026), A Non-Covalent Inhibitor of Wild-Type and C481S Mutated Bruton Tyrosine Kinase for B-Cell Malignancies: Efficacy and Safety of the Phase 2 Dose-Expansion Bellwave-001 Study". HemaSphere. 6: 578–579. doi: 10.1097/01.HS9.0000845612.25766.0c . S2CID   250001988.
• Reiff, Sean D.; Mantel, Rose; Smith, Lisa L.; Greene, J.T.; Muhowski, Elizabeth M.; Fabian, Catherine A.; Goettl, Virginia M.; Tran, Minh; Harrington, Bonnie K.; Rogers, Kerry A.; Awan, Farrukh T.; Maddocks, Kami; Andritsos, Leslie; Lehman, Amy M.; Sampath, Deepa; Lapalombella, Rosa; Eathiraj, Sudharshan; Abbadessa, Giovanni; Schwartz, Brian; Johnson, Amy J.; Byrd, John C.; Woyach, Jennifer A. (1 October 2018). "The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation". Cancer Discovery. 8 (10): 1300–1315. doi: 10.1158/2159-8290.CD-17-1409 . PMC   6261467 . PMID   30093506.
• Woyach, Jennifer A.; Flinn, Ian W.; Awan, Farrukh T.; Eradat, Herbert; Brander, Danielle; Tees, Michael; Parikh, Sameer A.; Phillips, Tycel J.; Ghori, Razi; Reddy, Nishitha M.; Farooqui, Mohammed Z.H.; Byrd, John C.; Stephens, Deborah M. (15 November 2022). "Efficacy and Safety of Nemtabrutinib, a Wild-Type and C481S-Mutated Bruton Tyrosine Kinase Inhibitor for B-Cell Malignancies: Updated Analysis of the Open-Label Phase 1/2 Dose-Expansion Bellwave-001 Study". Blood. 140 (Supplement 1): 7004–7006. doi: 10.1182/blood-2022-163596 . S2CID   256785160.
• Woyach, Jennifer A.; Stephens, Deborah M.; Flinn, Ian W.; Bhat, Seema A.; Savage, Ronald E.; Chai, Feng; Eathiraj, Sudharshan; Reiff, Sean D.; Muhowski, Elizabeth M.; Granlund, Lindsey; Szuszkiewicz, Lyndsey; Wang, Wayne; Schwartz, Brian; Ghori, Razi; Farooqui, Mohammed Z. H.; Byrd, John C. (6 November 2023). "First in Human Study of the Reversible BTK Inhibitor Nemtabrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia and B-Cell Non-Hodgkin Lymphoma". Cancer Discovery. 14 (1): 66–75. doi:10.1158/2159-8290.CD-23-0670. ISSN   2159-8290. PMID   37930156. S2CID   265032444.