ISDA: 9TBM

Deposition Date 2025-11-20

Release Date 2026-04-22

Last Version Date 2026-05-06

Entry Detail

PDB ID:

9TBM

Keywords:

SIGNALING PROTEIN

Title:

From KRASG12D to pan-KRAS inhibitors

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Escherichia coli bl21(de3)

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

1.60 Å

R-Value Free:

0.25

R-Value Work:

0.19

R-Value Observed:

0.20

Space Group:

P 1 21 1

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Isoform 2B of GTPase KRas
Gene (Uniprot):KRAS
Mutagens:G12D
Chain IDs:A, B, C
Chain Length:189
Number of Molecules:3
Biological Source:Homo sapiens

UniProt ID:P01116 Pfam ID:PF00071 EC:3.6.5.2

Ligand Molecules

A1JU5

GDP

Primary Citation

From KRAS G12D to Pan-KRAS Inhibitors─A Journey Enabled by Synthetic Innovation and Structure-Based Drug Design.

Ma, X, Sloman, D.L, Henderson, T.J, Bennett, D.J, Chessari, G, Day, P.J, Duggal, R, Edelstein, E, Gathiaka, S, Hoover, A, Howard, S, Kawamura, S, Kobayakawa, Y, Lacey, B.M, Lyons, T.W, Mansueto, M.S, Miller, R, Mizuarai, S, Munsell, E.V, O'Reilly, M, Oshima, T, Otte, R.D, Palani, A, Rees, D.C, Sagara, T, Sather, A, Schopf, P, Shibata, K, Shikata, Y, Solban, N, Venkataraman, S, Su, D, Swaminathan, U, Ye, Y, Stoeck, A, Han, Y.Show

J.Med.Chem. 69 9215 9241 (2026)

PMID: 41954203 DOI: 10.1021/acs.jmedchem.5c03662

Abstact

KRAS, a significant oncology target, has been challenging to develop drugs for until recent discoveries of KRAS(G12C) mutant-specific covalent inhibitors, including MK-1084. This article describes efforts toward the discovery of KRAS(G12D) mutant-specific inhibitors and how synthetic innovations and structure-based drug design were utilized to facilitate the discovery of pan-KRAS inhibitors.

Legend

Protein

Chemical

Disease

Primary Citation of related structures

Abstact

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