arm1

ARM1 is a potent inhibitor of aminopeptidase and epoxide hydrolase. The IC50 values are 7.61 µM for aminopeptidase and 12.4 µM for epoxide hydrolase.

CARM1-IN-1 (CARM1-IN-7G) is a selective inhibitor of CARM1 with IC50 of 8.6 μM. CARM1-IN-1 shows weak activity against PRMT1 and SET7 with IC50 > 600 μM.

PROTAC CARM1/IKZF3 degrader-1 (Compound 074) inhibits CARM1, reducing the methylation level of its substrate BAF155. This PROTAC degrader works by degrading IKZF 1/3 via a CRBN-dependent mechanism. It suppresses MYC protein expression, thereby inhibiting the proliferation of various multiple myeloma cells. Additionally, PROTAC CARM1/IKZF3 degrader-1 can induce apoptosis in H929 cells and overcomes resistance to immunomodulatory drugs (IMiDs, such as pomalidomide). It is applicable for cancer and immunology research. (Pink: ligand for target protein CARM1/IKZF3 ligand 1; Active form of target protein ligand: EZM 2302; Black: linker; Blue: ligand for E3 ligase Cereblon Thalidomide 4-fluoride)

CARM1/IKZF3 ligand 1 functions as an inhibitor of CARM1 and serves as a target protein ligand for the synthesis of PROTAC CARM1/IKZF3 degrader-1.

SARM1-IN-4 (Compound 7) is an orally active SARM1 inhibitor that reduces plasma neurofilament light chain (NfL) levels in a mouse model following a 50 mg/kg oral dose. By inhibiting the NAD+ hydrolase activity of SARM1, it prevents programmed axon degeneration, making it useful for research in neurodegenerative and neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and peripheral neuropathy.

SARM1-IN-5 (compound 1-23-a) is an inhibitor of SARM1, useful for researching diseases related to axonal degeneration, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).

CARM1/HDAC2-IN-1 (Compound CH-1) is a dual inhibitor targeting CARM1 and HDAC2, with IC50 values of 3.71 nM and 4.07 nM, respectively. This compound exhibits antitumor activity.

CARM1-IN-5 (Compound 17e) is a potent and selective inhibitor of CARM1, exhibiting an IC50 of 2 nM. By directly interacting with CARM1, CARM1-IN-5 effectively inhibits the methylation of substrate proteins. Additionally, CARM1-IN-5 demonstrates significant antiproliferative effects on melanoma cell lines.

ARM165 is a heterobifunctional molecule that degrades the protein PIK3CG and inhibits the PI3Kγ-Akt signaling pathway, thereby exerting anti-leukemic effects. It is capable of suppressing the proliferation of AML cells, with an IC50 of less than 1 μM.

SARM1-IN-6 (Compound 17a) is a brain-penetrant orthosteric inhibitor of SARM1. It exhibits an IC50 of 14 nM against NAM and 74 nM against HEK cells.

SARM1-IN-7 is a potent, orally active inhibitor of SARM1, targeting its active site (orthosteric). This compound persistently enhances SARM1's enzymatic activity, leading to exacerbated NAD depletion at suboptimal concentrations. In both cell and mouse models with activated SARM1, SARM1-IN-7 exhibits dual effects: high doses provide cell/neuron protection, whereas low doses intensify cell/neuron damage. SARM1-IN-7 is applicable in studies of axonal degeneration.

CARM1-IN-6 (Compound iCARM1) dihydrochloride is a potent and selective inhibitor of CARM1, with an IC50 value of 12.3 μM. It demonstrates cell growth inhibitory activity and is applicable in cancer research.

SARM1-IN-8 (compound 6) is a competitive base-exchange inhibitor of SARM1. It competitively inhibits the activity of the NAD+ substrate SARM1Δ1-27.

SARM1-IN-2 is a potent SARM1 inhibitor for the study of metabolic and neurological related diseases.

CARM1-IN-3 dihydrochloride (compound 17b) is a potent and selective coactivator-associated arginine methyltransferase inhibitor, targeting CARM1 with an IC50 of 0.07 μM and exhibiting minimal activity on CARM3 (IC50 > 25 μM).

CARM1-IN-1 hydrochloride is a potent and selective inhibitor of CARM1 (IC50: 8.6 μM) with minimal inhibition of PRMT1 and SET7.

CARM1-IN-3 (compound 17b) is a potent and selective inhibitor of co-activator associated arginine methyltransferase (CARM1), with IC50 values of 0.07 µM for CARM1 and greater than 25 µM for CARM3 [1].

PROTAC CARM1 degrader-1 (compound 3b) is a highly potent degrader (DC50=8.1 nM) of the co-activator associated arginine methyltransferase (CARM1), facilitating its degradation via the VHL-proteasome pathway. By degrading CARM1, it reduces methylation of substrates, such as poly(A)-binding protein PABP1 and BGR1-associated factor BAF155, inhibiting breast cancer cell migration [1].

PROTAC CARM1 degrader-2 (compound 3e), with a DC50 value of 8.8 nM, is a VHL- and proteasome-dependent degrader of co-activator associated arginine methyltransferase (CARM1). It promotes the degradation of CARM1 and prevents the methylation of its substrates, including poly(A)-binding protein PABP1 and BGR1-associated factor BAF155, consequently inhibiting breast cancer cell migration [1].

CARM1-IN-4 (compound 11f) serves as a potent inhibitor of CARM1, exhibiting IC50 values of 9 nM for CARM1 and 56 nM for PRMT1. This compound significantly inhibits the proliferation of colorectal cancer cell lines and curtails the methyltransferase activity of CARM1, blocking the methylation of downstream proteins. Moreover, CARM1-IN-4 induces apoptosis and demonstrates notable antitumor activity [1].

CARM1-IN-6 (iCARM1) is a potent and selective inhibitor of CARM1. It possesses activity that inhibits cell growth and is applicable for cancer research.

SARM1-IN-3 (Example 30) is an inhibitor of SARM1. This compound is employed in the study of chemotherapy-induced peripheral neuropathy (CIPN).

DC_C66 DC_C66 has good selectivity for CARM1, PRMT1 (IC50 = 21μM), PRMT6 (IC50 = 47μM) and PRMT5. It is a cell-permeable, selective co-activator related arginine methyltransferase 1 (CARM1) inhibitor with IC50 of 1.8 μM.

Isoquinoline, 5-iodo- is a potent and selective inhibitor of SARM1(IC50 = 75 nM) by preventing axonal degeneration and by allowing functional recovery of a metastable pool of damaged, but viable, axons.