Drug Information

Drug (ID: DG01891) and It's Reported Resistant Information

• Name: SHP099
• Synonyms: SHP099
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Acute myeloid leukemia [ICD-11: 2A60]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Colorectal cancer [ICD-11: 2B91]; [2]
• Target: .; NOUNIPROTAC; [2]

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Acute myeloid leukemia [ICD-11: 2A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [1]

• Molecule Alteration: Missense mutation; p.E76K (c.226G>A)
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TF-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0559

Key Molecule: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [1]

• Molecule Alteration: Missense mutation; p.D61Y (c.181G>T)
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TF-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0559

Key Molecule: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [1]

• Molecule Alteration: Missense mutation; p.A72V (c.215C>T)
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TF-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0559

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [1]

• Molecule Alteration: Missense mutation; p.E69K (c.205G>A)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TF-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0559

Hematologic cancer [ICD-11: 2B3Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [2]

• Molecule Alteration: Missense mutation; p.V617F (c.1849G>T)
• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: RAS/ERK signaling pathway; Inhibition; hsa01521
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: NCI-H2228 cells; Lung; Homo sapiens (Human); CVCL_1543
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: KYSE520 cells; Esophagus; Homo sapiens (Human); CVCL_1355
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: Sum52 cells; Pleural effusion; Homo sapiens (Human); CVCL_3425
• In Vitro Model: NCI-H2170 cells; Lung; Homo sapiens (Human); CVCL_1535
• In Vitro Model: NCI-H2170 cells; Lung; Homo sapiens (Human); CVCL_1535
• In Vitro Model: H293 cells; Kidney; Homo sapiens (Human); N.A.
• In Vivo Model: Athymic nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: CellTitre-Glo assay; Crystal violet staining assay
• Mechanism Description: SHP099 suppresses RAS-ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models.

Colorectal cancer [ICD-11: 2B91]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: RAS/ERK signaling pathway; Inhibition; hsa01521
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: NCI-H2228 cells; Lung; Homo sapiens (Human); CVCL_1543
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: KYSE520 cells; Esophagus; Homo sapiens (Human); CVCL_1355
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: Sum52 cells; Pleural effusion; Homo sapiens (Human); CVCL_3425
• In Vitro Model: NCI-H2170 cells; Lung; Homo sapiens (Human); CVCL_1535
• In Vitro Model: NCI-H2170 cells; Lung; Homo sapiens (Human); CVCL_1535
• In Vitro Model: H293 cells; Kidney; Homo sapiens (Human); N.A.
• In Vivo Model: Athymic nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: CellTitre-Glo assay; Crystal violet staining assay
• Mechanism Description: SHP099 suppresses RAS-ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models.

References

• Ref 1: Selective inhibition of leukemia-associated SHP2(E69K) mutant by the allosteric SHP2 inhibitor SHP099Leukemia. 2018 May;32(5):1246-1249. doi: 10.1038/s41375-018-0020-5. Epub 2018 Jan 30.
• Ref 2: Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinasesNature. 2016 Jul 7;535(7610):148-52. doi: 10.1038/nature18621. Epub 2016 Jun 29.