Md Abdullah Al Noman

All Publications

• The molecular basis for nuclear pore destruction by a proximity-inducing molecular glue. Cell chemical biology Hinshaw, S. M., Yuan, L., Noman, M. A., Martinez, M. J., Colombo, G. M., Dwyer, B. G., Ji, W., Romero, B. A., Forrest, I., Lu, J., Bian, J., Dunn, T. B., Garvin, E. R., Fernandez, D., Zhang, T., Gray, N. S., Corsello, S. M. 2026

  Abstract

  Molecular glues that induce new protein interactions can be potent therapeutics. We and others recently discovered that the small molecule PRLX-93936 (PRLX), which was originally developed as an erastin derivative with antitumor activity, is a molecular glue that alters the substrate specificity of the TRIM21 ubiquitin ligase. PRLX causes TRIM21 to bind the nuclear pore protein NUP98, triggering nuclear pore complex (NPC) degradation. We present here the structural and biochemical basis of NUP98 recognition, finding that ternary complex assembly depends on the creation of a composite TRIM21-small molecule surface competent for NUP98 binding. A scarcity of direct small molecule-NUP98 contacts likely explains how multiple structurally diverse TRIM21 ligands can induce NPC degradation. We also report the discovery of an enhanced molecular glue, MAN-021, and describe its structure. Our findings provide a basis for rational development of next-generation small molecules with enhanced or differentiated activities.

  View details for DOI 10.1016/j.chembiol.2026.04.016

  View details for PubMedID 42202785

• From Discovery to Clinical Trial: YCT-529, an Oral NonHormonal Male Contraceptive Targeting the Retinoic Acid Receptor Alpha (vol 69, pg 1568, 2026) JOURNAL OF MEDICINAL CHEMISTRY Shi, R., Al Noman, M., Mannowetz, N., Cheryala, N., Haque, E., Taher, N., Maitra, S., Naqvi, T., Chung, S. S. W., Bakshi, A., Hawkinson, J. E., Wong, H. L., Wolgemuth, D. J., Georg, G. I. 2026; 69 (5): 6295

  View details for DOI 10.1021/acs.jmedchem.6c00520

  View details for Web of Science ID 001706048700001

  View details for PubMedID 41773782

  View details for PubMedCentralID PMC12990025

• From Discovery to Clinical Trial: YCT-529, an Oral NonHormonal Male Contraceptive Targeting the Retinoic Acid Receptor Alpha JOURNAL OF MEDICINAL CHEMISTRY Shi, R., Al Noman, M., Mannowetz, N., Cheryala, N., Haque, E., Maitra, S., Naqvi, T., Chung, S. S. W., Bakshi, A., Hawkinson, J. E., Wong, H. L., Wolgemuth, D. J., Georg, G. I. 2026

  Abstract

  The retinoic acid receptor alpha (RARα) has emerged as a compelling genetically and pharmacologically validated target for nonhormonal male contraception due to its essential role in spermatogenesis. In the present study, a search for specific inhibitors of RARα utilized systematic linker bioisosterism, hydrophobic core modification, and iterative structure-activity relationship refinement, identified the acid 9, a pyrrole-linked analog that potently inhibits RARα (IC50 = 1.2 nM) with >300-fold selectivity over RARβ and RARγ. Sprague-Dawley rat studies with the sodium salt of 9, YCT-529, showed good oral bioavailability and dose-proportional pharmacokinetics without drug accumulation after 28 days of dosing. Once-daily oral administration (0.75 mg/kg for 28 days) reversibly suppressed epididymal sperm counts and fertility in rats, with a no-observed-adverse-effect level at 30 mg/kg (highest dose tested), affording a ≥40-fold therapeutic window. These findings validated aromatic linker substitution as a powerful design strategy for identifying RARα antagonists and led to the clinical advancement of YCT-529 as a nonhormonal male contraceptive.

  View details for DOI 10.1021/acs.jmedchem.5c03051

  View details for Web of Science ID 001660633500001

  View details for PubMedID 41524264