Drug Information

Drug (ID: DG01524) and It's Reported Resistant Information

• Name: Ulixertinib
• Synonyms: Ulixertinib; 869886-67-9; VRT752271; BVD-523; Ulixertinib (BVD-523); UNII-16ZDH50O1U; Ulixertinib [INN]; 16ZDH50O1U; CHEMBL3590106; Ulixertinib (INN); 869886-67-9 (free base); VRT-752271; Ulixertinib (BVD-523, VRT752271); (S)-4-(5-chloro-2-(isopropylamino)pyridin-4-yl)-N-(1-(3-chlorophenyl)-2-hydroxyethyl)-1H-pyrrole-2-carboxamide; (S)-4-(5-chloro-2-(isopropylamino)pyridin-4-yl)-N-(1-(3-chlorophenyl)-2-hydroxyethyl)-1H-pyrrole-2-carboxamide.; 4-[5-chloranyl-2-(propan-2-ylamino)pyridin-4-yl]-~{N}-[(1~{S})-1-(3-chlorophenyl)-2-oxidanyl-ethyl]-1~{H}-pyrrole-2-carboxamide; N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-chloro-2-(propan-2-ylamino)pyridin-4-yl]-1H-pyrrole-2-carboxamide; BVD-ERK; Ulixertinib (BVD-523,VRT752271); 4-(5-chloro-2-(isopropylamino)pyridin-4-yl)-N-((S)-1-(3-chlorophenyl)-2-hydroxyethyl)-1H-pyrrole-2-carboxamide; BVD523 HCl; BVD-523 HCl; VRT752271 HCl; GTPL9210; SCHEMBL14211742; BCP04232; EX-A1332; BDBM50094465; NSC797771; NSC800959; s7854; ZINC34642570; AKOS025396467; CCG-269049; DB13930; NSC-797771; NSC-800959; NCGC00378692-02; NCGC00378692-05; NCGC00378692-07; 1H-Pyrrole-2-carboxamide, 4-(5-chloro-2-((1-methylethyl)amino)-4-pyridinyl)-N-((1S)-1-(3-chlorophenyl)-2-hydroxyethyl)-; AC-33165; AS-56114; HY-15816; QC-10489; BCP0726000085; D11038; J-690368; Q27089081; 3,5-Dichloro-2-hydroxy-N-(4-methoxy-3-biphenylyl)benzenesulfonamide; 4-[5-Chloro-2-(isopropylamino)-4-pyridinyl]-N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
• Target: .; NOUNIPROTAC; [1]
• Formula: 7
• IsoSMILES: CC(C)NC1=NC=C(C(=C1)C2=CNC(=C2)C(=O)N[C@H](CO)C3=CC(=CC=C3)Cl)Cl
• InChI: InChI=1S/C21H22Cl2N4O2/c1-12(2)26-20-8-16(17(23)10-25-20)14-7-18(24-9-14)21(29)27-19(11-28)13-4-3-5-15(22)6-13/h3-10,12,19,24,28H,11H2,1-2H3,(H,25,26)(H,27,29)/t19-/m1/s1
• InChIKey: KSERXGMCDHOLSS-LJQANCHMSA-N
• PubChem CID: 11719003
• DrugBank ID: DB13930

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

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: FGFR-tacc positive glioblastoma [ICD-11: 2A00.01]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010

Small intestine carcinoma [ICD-11: 2B80]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Molecule Alteration: Missense mutation; p.G469A (c.1406G>C)
• Sensitive Disease: Small intestine carcinoma [ICD-11: 2B80.20]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity 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)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• 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: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• In Vitro Model: G-361 cells; Skin; Homo sapiens (Human); CVCL_1220
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vivo Model: Athymic nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Standard coupled-enzyme assay

Gallbladder cancer [ICD-11: 2C13]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Molecule Alteration: Missense mutation; p.L485W (c.1454T>G)
• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Experimental Note: Identified from the Human Clinical Data

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Molecule Alteration: Missense mutation; p.L597Q (c.1790T>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010

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

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010

Melanoma [ICD-11: 2C30]

Drug Sensitivity 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)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• 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: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• In Vitro Model: G-361 cells; Skin; Homo sapiens (Human); CVCL_1220
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vivo Model: Athymic nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Standard coupled-enzyme assay

Head and neck cancer [ICD-11: 2D42]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Molecule Alteration: Missense mutation; p.G469A (c.1406G>C)
• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010

References

• Ref 1: First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion StudyCancer Discov. 2018 Feb;8(2):184-195. doi: 10.1158/2159-8290.CD-17-1119. Epub 2017 Dec 15.
• Ref 2: Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib)Mol Cancer Ther. 2017 Nov;16(11):2351-2363. doi: 10.1158/1535-7163.MCT-17-0456. Epub 2017 Sep 22.