Drug Information

Drug (ID: DG01645) and It's Reported Resistant Information

• Name: PLX7904
• Synonyms: PLX7904; 1393465-84-3; PB04; PLX-7904; 5-(2-Cyclopropylpyrimidin-5-yl)-3-[3-[[ethyl(methyl)sulfamoyl]amino]-2,6-difluorobenzoyl]-1H-pyrrolo[2,3-b]pyridine; N'-(3-{[5-(2-Cyclopropylpyrimidin-5-Yl)-1h-Pyrrolo[2,3-B]pyridin-3-Yl]carbonyl}-2,4-Difluorophenyl)-N-Ethyl-N-Methylsulfuric Diamide; Sulfamide, N'-[3-[[5-(2-cyclopropyl-5-pyrimidinyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-N-ethyl-N-methyl-; CHEMBL4206836; SCHEMBL15667328; BDBM317744; PLX7904(PB04); BCP18248; EX-A2872; s7964; ZINC144822687; CCG-269789; CS-5129; US9624213, Compound P-0240; HY-18997; A901658; Q27456931; ({3-[5-(2-cyclopropylpyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}sulfamoyl)(ethyl)methylamine; N'-[3-[[5-(2-cyclopropyl-5-pyrimidinyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-N-ethyl-N-methyl-sulfamide
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Melanoma [ICD-11: 2C30]; [1]
• Target: .; NOUNIPROTAC; [1]
• Formula: 8
• IsoSMILES: CCN(C)S(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=C2C=C(C=N3)C4=CN=C(N=C4)C5CC5)F
• InChI: InChI=1S/C24H22F2N6O3S/c1-3-32(2)36(34,35)31-19-7-6-18(25)20(21(19)26)22(33)17-12-30-24-16(17)8-14(9-29-24)15-10-27-23(28-11-15)13-4-5-13/h6-13,31H,3-5H2,1-2H3,(H,29,30)
• InChIKey: DKNZQPXIIHLUHU-UHFFFAOYSA-N
• PubChem CID: 90116945

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: SkMEL239-C3 cells; Skin; Homo sapiens (Human); CVCL_6122
• In Vitro Model: SkMEL239 cells; Skin; Homo sapiens (Human); CVCL_6122
• In Vitro Model: IPC-298 cells; Skin; Homo sapiens (Human); CVCL_1307
• In Vitro Model: Colo829 cells; Skin; Homo sapiens (Human); CVCL_1137
• In Vitro Model: B9 cells; N.A.; Mus musculus (Mouse); CVCL_1952
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Microarray gene expression analysis; Crystallization and structure determination assay
• Experiment for Drug Resistance: CellTiter-Glo assay; Anchorage-independent growth assay

Melanoma [ICD-11: 2C30]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Molecule Alteration: Missense mutation; p.G466E (c.1397G>A)
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: 8505C cells; Thyroid; Homo sapiens (Human); CVCL_1054
• In Vitro Model: Hth104 cells; Thyroid gland; Homo sapiens (Human); CVCL_A427
• In Vivo Model: mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.G466E (c.1397G>A) in gene BRAF cause the resistance of PLX7904 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Molecule Alteration: Missense mutation; p.V600R (c.1798_1799delGTinsAG)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: 8505C cells; Thyroid; Homo sapiens (Human); CVCL_1054
• In Vitro Model: Hth104 cells; Thyroid gland; Homo sapiens (Human); CVCL_A427
• In Vivo Model: mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.V600R (c.1798_1799delGTinsAG) in gene BRAF cause the sensitivity of PLX7904 by aberration of the drug's therapeutic target

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Molecule Alteration: Missense mutation; p.V600D (c.1799_1800delTGinsAC)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: 8505C cells; Thyroid; Homo sapiens (Human); CVCL_1054
• In Vitro Model: Hth104 cells; Thyroid gland; Homo sapiens (Human); CVCL_A427
• In Vivo Model: mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.V600D (c.1799_1800delTGinsAC) in gene BRAF cause the sensitivity of PLX7904 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: SkMEL239-C3 cells; Skin; Homo sapiens (Human); CVCL_6122
• In Vitro Model: SkMEL239 cells; Skin; Homo sapiens (Human); CVCL_6122
• In Vitro Model: IPC-298 cells; Skin; Homo sapiens (Human); CVCL_1307
• In Vitro Model: Colo829 cells; Skin; Homo sapiens (Human); CVCL_1137
• In Vitro Model: B9 cells; N.A.; Mus musculus (Mouse); CVCL_1952
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Microarray gene expression analysis; Crystallization and structure determination assay
• Experiment for Drug Resistance: CellTiter-Glo assay; Anchorage-independent growth assay

References

• Ref 1: An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF SignalingCancer Cell. 2016 Sep 12;30(3):485-498. doi: 10.1016/j.ccell.2016.06.024. Epub 2016 Aug 11.
• Ref 2: RAF inhibitors that evade paradoxical MAPK pathway activationNature. 2015 Oct 22;526(7574):583-6. doi: 10.1038/nature14982. Epub 2015 Oct 14.