Drug Information

Drug (ID: DG01579) and It's Reported Resistant Information

• Name: JQ1
• Synonyms: 1268524-70-4; (+)-JQ1; (+)-JQ-1; JQ1 compound; JQ1; JQ-1; (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-triMethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate; UNII-1MRH0IMX0W; (S)-JQ1; Bromodomain Inhibitor, (+)-JQ1; 1MRH0IMX0W; C23H25ClN4O2S; CHEMBL1957266; tert-butyl (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate; (S)-(+)-tert-Butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate; 6H-Thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine-6-acetic acid, 4-(4-chlorophenyl)-2,3,9-trimethyl-, 1,1-dimethylethyl ester, (6S)-; 6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, 4-(4-chlorophenyl)-2,3,9-trimethyl-, 1,1-dimethylethyl ester, (6S)-; tert-Butyl 2-((6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-6-yl)acetate; (S)-(+)-tert-Butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-6-yl)acetate; 3mxf; 4flp; 4qzs; (6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid 1,1-dimethylethyl ester; tert-butyl 2-((6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate; MLS006011158; SCHEMBL881227; GTPL7511; CHEBI:95080; DTXSID20155309; EX-A457; SYN3004; CHEBI:137113; BDBM50365262; NSC760183; NSC764043; s7110; ZINC57318556; AKOS016344680; (+)JQ-1; CCG-269306; CS-0581; JQ1 (+); JQ1-(+); NSC-760183; NSC-764043; NCGC00250412-01; NCGC00250412-15; NCGC00250412-21; (S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-triMethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diaz; AC-32617; AS-16352; BP-21590; HY-13030; SMR004702930; BB 0262647; (+)-JQ1, >=98% (HPLC); A854208; Q3156953; (6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]di azepine-6-acetic acid 1,1-dimethylethyl ester; tert-butyl (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate;(S)-(+)-tert-Butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate; tert-butyl [(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetate; tert-butyl 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate; tert-butyl[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetate
• Indication:
  In total 1 Indication(s)
  Myelofibrosis [ICD-11: 2A20]; Phase 1; [1]
• Target: Janus kinase 2 (JAK-2); JAK2_HUMAN; [2]
• Formula: 5
• IsoSMILES: CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)OC(C)(C)C)C4=CC=C(C=C4)Cl)C
• InChI: InChI=1S/C23H25ClN4O2S/c1-12-13(2)31-22-19(12)20(15-7-9-16(24)10-8-15)25-17(11-18(29)30-23(4,5)6)21-27-26-14(3)28(21)22/h7-10,17H,11H2,1-6H3/t17-/m0/s1
• InChIKey: DNVXATUJJDPFDM-KRWDZBQOSA-N
• PubChem CID: 46907787
• ChEBI ID: CHEBI:95080
• TTD Drug ID: D00MYW

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [1]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.A459V (c.1376C>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Carcinoma tissue basal cell; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.A459V (c.1376C>T) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [1]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C469Y (c.1406G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Carcinoma tissue basal cell; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.C469Y (c.1406G>A) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [1]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T241M (c.722C>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Carcinoma tissue basal cell; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.T241M (c.722C>T) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [1]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W281C (c.843G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Carcinoma tissue basal cell; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.W281C (c.843G>T) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [1]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V321M (c.961G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Carcinoma tissue basal cell; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.V321M (c.961G>A) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Pancreatic cancer [ICD-11: 2C10]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: M-phase inducer phosphatase 2 (CDC25B) [3]

• Sensitive Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: MiaPaCa-2 cells; Blood; Homo sapiens (Human); CVCL_0428
• In Vitro Model: BxPc3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vivo Model: SCID CB 17-/- female mice model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemistry; Immunoblotting assay
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Results: Immunohistochemical data demonstrated that levels of CDC25B differed by ~2- to 5-fold in cell lines and PDX models used. In vitro data showed that the level of CDC25B paralleled sensitivity to JQ1. Similarly, in vivo data showed that tumors with high-level CDC25B were more sensitive to JQ1 than tumors with lower CDC25B. The combination of JQ1 + a pan CDC25 inhibitor was synergistic in gemcitabine-resistant Panc1.gemR cells that had relatively high levels of CDC25B expression compared to parent cells. Conclusion: The data suggest that CDC25B may be an independent indicator of sensitivity to BET inhibitors and that CDC25B may contribute to gemcitabine insensitivity in this tumor type.

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Hepatocyte growth factor receptor (MET) [4]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: HGF-Met signaling pathway; Regulation; N.A.
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Calu-1 cells; Lung; Homo sapiens (Human); CVCL_0608
• In Vitro Model: H157 cells; Lung; Homo sapiens (Human); CVCL_2458
• In Vitro Model: NCI- H460 cells; Pleural effusion; Homo sapiens (Human); CVCL_0459
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Sulforhodamine B assay
• Mechanism Description: JQ1, I-BET151, or BRD4 silencing all downregulated Met and inhibited both NSCLC cell viability in vitro and tumor growth in vivo.The inhibitory influences of JQ1 on the activity of PI3K/Akt and ERK pathways and cell growth were countervailed by HGF.

Ovarian cancer [ICD-11: 2C73]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: AT-rich interactive domain-containing protein 1A (ARID1A) [2]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Nonsense; p.Q1148* (c.3442C>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: TOV21G cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: OVCA429 cells; Ovary; Homo sapiens (Human); CVCL_3936
• In Vitro Model: TUOC1 cells; Ovary; Homo sapiens (Human); CVCL_L700
• In Vitro Model: SMOV2 cells; Ovary; Homo sapiens (Human); CVCL_S920
• In Vitro Model: RMGII cells; Ascites; Homo sapiens (Human); CVCL_2803
• In Vitro Model: RMGI cells; Ascites; Homo sapiens (Human); CVCL_1662
• In Vitro Model: OVTOKO cells; Spleen; Homo sapiens (Human); CVCL_3117
• In Vitro Model: OVMANA cells; Ovary; Homo sapiens (Human); CVCL_3111
• In Vitro Model: OVAS cells; Ascites; Homo sapiens (Human); CVCL_0V12
• In Vitro Model: OV207 cells; Ovary; Homo sapiens (Human); CVCL_A404
• In Vitro Model: KOC7C cells; Pleural effusion; Homo sapiens (Human); CVCL_5307
• In Vitro Model: HAC2 cells; Ascites; Homo sapiens (Human); CVCL_8354
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The inhibitory effects on residual SWI/SNF function, specifically via reduced ARID1B expression, may explain the enhanced sensitivity of ARID1A mutant cells to BET inhibitors.

References

• Ref 1: Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma. Cancer Cell. 2015 Mar 9;27(3):327-41. doi: 10.1016/j.ccell.2015.02.001.
• Ref 2: ARID1A mutation sensitizes most ovarian clear cell carcinomas to BET inhibitorsOncogene. 2018 Aug;37(33):4611-4625. doi: 10.1038/s41388-018-0300-6. Epub 2018 May 15.
• Ref 3: The BET inhibitor sensitivity is associated with the expression level of CDC25B in pancreatic cancer models. Cancer Drug Resist. 2024 Oct 18;7:40.
• Ref 4: Targeting BET proteins inhibited the growth of non-small cell lung carcinoma through downregulation of Met expression. Cell Biol Int. 2023 Mar;47(3):622-633.