Lorundrostat

Lorundrostat
Clinical data
Other names	MLS 101
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name N-(4-Acetamidocyclohexyl)-2-[4-[5-(4-methylphenyl)-1,2,4-triazin-3-yl]piperazin-1-yl]acetamide;
CAS Number	1820940-17-7;
PubChem CID	126567187;
ChemSpider	123963150;
UNII	KA8W5LDS6Z;
KEGG	D12773;
ChEMBL	ChEMBL5095105;
Chemical and physical data
Formula	C24H33N7O2
Molar mass	451.575 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC=C(C=C1)C2=CN=NC(=N2)N3CCN(CC3)CC(=O)NC4CCC(CC4)NC(=O)C;
	InChI InChI=1S/C24H33N7O2/c1-17-3-5-19(6-4-17)22-15-25-29-24(28-22)31-13-11-30(12-14-31)16-23(33)27-21-9-7-20(8-10-21)26-18(2)32/h3-6,15,20-21H,7-14,16H2,1-2H3,(H,26,32)(H,27,33); Key:YHGVDZULVMINCJ-UHFFFAOYSA-N;

Lorundrostat (developmental name MLS 101) is an aldosterone synthase inhibitor developed by Mineralys Therapeutics for high blood pressure. In clinical trials as an add-on medication for people with uncontrolled hypertension, decreased renin and elevated aldosterone it significantly reduced blood pressure. Hyperkalemia occurred in some trial participants.^[1]^[2]^[3]^[4]

In a meta-analysis analysing data from 3 randomized controlled trials over 3 months of clinical use, lorundrostat at 50-100mg/day was found to be effective in lowering blood pressure, with associated issues of mild increase in serum potassium levels and decline in the glomerular filtration rate ^[5]

References

↑ Laffin, Luke J.; Rodman, David; Luther, James M.; Vaidya, Anand; Weir, Matthew R.; Rajicic, Natasa; Slingsby, B. T.; Nissen, Steven E.; Beasley, Richard; Budoff, Matthew; Carr, George; Carroll, Michael; Cevallos Yepez, Jose; Chhabra, Anil; Cole, Frank; Dunn, Leonard; Eaves, William; Ebuh, Valentine; Estevez, Roger; Gould, Glenn; Hong, Matthew; Iteld, Bruce; Jain, Mahendra; Kemp, Charles; Kennelly, Christina; Kleiner, Mark; Kutner, Mark; Laffin, Luke; Lambert, Joseph; Ledesma, Gilbert; Lee, Keung; Lentz, John; Lupovitch, Steven; Luther, James; Lynn, Lon; Marquez, Obadias; Mazhar, Mobeen; Morin, David; Neutel, Joel; Oppong, Yaa; Osorio, Merlin; Patron, Andres; Pharr, Walter; Ponce de Leon, Mercedes; Rodriguez-Ables, Lilia; Rosen, Jeffrey; Sachmechi, Issac; Surowitz, Ronald; Wadsworth, Larkin; Wayne, Jeffrey; Zafar, Zahid (26 September 2023). "Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension: The Target-HTN Randomized Clinical Trial". JAMA. 330 (12): 1140–1150. doi:10.1001/jama.2023.16029. ISSN 0098-7484. PMC 10493865. PMID 37690061.
↑ Rodman, David; Weir, Matthew R.; Slingsby, Bt; Laffin, Luke; Nissen, Steven E. (March 2023). "Highly Effective Blood Pressure Lowering with MLS-101, A New Aldosterone Synthase Inhibitor, in Individuals with Obesity and Raas Dysregulation". Journal of the American College of Cardiology. 81 (8): 306. doi:10.1016/S0735-1097(23)00750-7. S2CID 257347846.
↑ Fujii, Aya; Hiraga, Yuki; Kawai, Mizue; Ogawa, Kei; Ohta, Yoshiyasu; Rahman, Sheikh Mohammed Ashfaq; Shimizu, Hidetoshi; Sugimoto-Kawabata, Kanami; Van Iersel, Mattheus (Thijs); Van Lier, Jan Jaap; Slingsby, Bt; Rodman, David (March 2023). "First-In-Human Study of MLS-101, A Potent and Highly Selective Aldosterone Synthase Inhibitor". Journal of the American College of Cardiology. 81 (8): 616. doi:10.1016/S0735-1097(23)01060-4. S2CID 257350703.
↑ Irfan, Hamza; Ahmed, Aliza; Nawani, Komal Devi (January 2024). "Hypertension and Lorundrostat: Key Discoveries From the TARGET-HTN Trial". Current Problems in Cardiology. 49 (1) 102144. doi:10.1016/j.cpcardiol.2023.102144. PMID 37858848. S2CID 264334619.
↑ Kamrul-Hasan AB, Chatterjee S, Nagendra L, Nair S, Dutta D, Pappachan JM (Jun 2026). "Safety and efficacy of lorundrostat, an aldosterone synthase inhibitor, in patients with uncontrolled hypertension: A systematic review and meta-analysis". Medicine (Baltimore). 105 (23) e49158. doi:10.1097/MD.0000000000049158. PMC 13246067. PMID 42260805.

[1] Laffin, Luke J.; Rodman, David; Luther, James M.; Vaidya, Anand; Weir, Matthew R.; Rajicic, Natasa; Slingsby, B. T.; Nissen, Steven E.; Beasley, Richard; Budoff, Matthew; Carr, George; Carroll, Michael; Cevallos Yepez, Jose; Chhabra, Anil; Cole, Frank; Dunn, Leonard; Eaves, William; Ebuh, Valentine; Estevez, Roger; Gould, Glenn; Hong, Matthew; Iteld, Bruce; Jain, Mahendra; Kemp, Charles; Kennelly, Christina; Kleiner, Mark; Kutner, Mark; Laffin, Luke; Lambert, Joseph; Ledesma, Gilbert; Lee, Keung; Lentz, John; Lupovitch, Steven; Luther, James; Lynn, Lon; Marquez, Obadias; Mazhar, Mobeen; Morin, David; Neutel, Joel; Oppong, Yaa; Osorio, Merlin; Patron, Andres; Pharr, Walter; Ponce de Leon, Mercedes; Rodriguez-Ables, Lilia; Rosen, Jeffrey; Sachmechi, Issac; Surowitz, Ronald; Wadsworth, Larkin; Wayne, Jeffrey; Zafar, Zahid (26 September 2023). "Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension: The Target-HTN Randomized Clinical Trial". JAMA. 330 (12): 1140–1150. doi:10.1001/jama.2023.16029. ISSN 0098-7484. PMC 10493865. PMID 37690061.

[2] Rodman, David; Weir, Matthew R.; Slingsby, Bt; Laffin, Luke; Nissen, Steven E. (March 2023). "Highly Effective Blood Pressure Lowering with MLS-101, A New Aldosterone Synthase Inhibitor, in Individuals with Obesity and Raas Dysregulation". Journal of the American College of Cardiology. 81 (8): 306. doi:10.1016/S0735-1097(23)00750-7. S2CID 257347846.

[3] Fujii, Aya; Hiraga, Yuki; Kawai, Mizue; Ogawa, Kei; Ohta, Yoshiyasu; Rahman, Sheikh Mohammed Ashfaq; Shimizu, Hidetoshi; Sugimoto-Kawabata, Kanami; Van Iersel, Mattheus (Thijs); Van Lier, Jan Jaap; Slingsby, Bt; Rodman, David (March 2023). "First-In-Human Study of MLS-101, A Potent and Highly Selective Aldosterone Synthase Inhibitor". Journal of the American College of Cardiology. 81 (8): 616. doi:10.1016/S0735-1097(23)01060-4. S2CID 257350703.

[4] Irfan, Hamza; Ahmed, Aliza; Nawani, Komal Devi (January 2024). "Hypertension and Lorundrostat: Key Discoveries From the TARGET-HTN Trial". Current Problems in Cardiology. 49 (1) 102144. doi:10.1016/j.cpcardiol.2023.102144. PMID 37858848. S2CID 264334619.

[5] Kamrul-Hasan AB, Chatterjee S, Nagendra L, Nair S, Dutta D, Pappachan JM (Jun 2026). "Safety and efficacy of lorundrostat, an aldosterone synthase inhibitor, in patients with uncontrolled hypertension: A systematic review and meta-analysis". Medicine (Baltimore). 105 (23) e49158. doi:10.1097/MD.0000000000049158. PMC 13246067. PMID 42260805.

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References