Drug Information

Drug (ID: DG01473) and It's Reported Resistant Information

• Name: 3-Deazaneplanocin
• Synonyms: 3-Deazaneplanocin; 3-Deazaneplanocin A; 102052-95-9; (1s,2r,5r)-5-(4-amino-1h-imidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol; 3-Deazaneplanocin,DZNep; 3-Deazaneplanocin-A; UNII-544SH4020S; DZNep; (1S,2R,5R)-5-(4-aminoimidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol; CHEMBL154745; 544SH4020S; 3-Deaza-neplanocin; c^Neplanocin A; 3-Deazaneplanocin A (DZNep) hydrochloride; 3-Deazaneplanocin A (DZNep; SCHEMBL863851; SCHEMBL12280736; DTXSID30144562; InSolution EZH2 Inhibitor, DZNep; AVS-4275; CEA05295; 3238AH; BDBM50096906; ZINC21290121; AKOS005146283; CS-0357; AC-27393; HY-10442; BRD-K77791657-001-01-1; Q15410156; (-)-1-[(1R,4R,5S)-3-(Hydroxymethyl)-4,5-dihydroxy-2-cyclopenten-1-yl]4-aminoimidazo[4,5-c]pyridine; 3-Cyclopentene-1,2-diol, 5-(4-amino-1H-imidazo(4,5-c)pyridiny-1-yl)-3-(hydroxymethyl)-, (1S-(alpha,2alpha,5beta))-
• Formula: 2
• IsoSMILES: C1=CN=C(C2=C1N(C=N2)[C@@H]3C=C([C@H]([C@H]3O)O)CO)N
• InChI: InChI=1S/C12H14N4O3/c13-12-9-7(1-2-14-12)16(5-15-9)8-3-6(4-17)10(18)11(8)19/h1-3,5,8,10-11,17-19H,4H2,(H2,13,14)/t8-,10-,11+/m1/s1
• InChIKey: OMKHWTRUYNAGFG-IEBDPFPHSA-N
• PubChem CID: 73087

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Diffuse large B-cell lymphoma [ICD-11: 2A81]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [1]

• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Molecule Alteration: Missense mutation; p.Y641N (c.1921T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: Chromatin Immunoprecipitation assay; Western blot analysis
• Experiment for Drug Resistance: Propidium-iodide cell cycle analysis; BrdU-PI cell cycle analysis

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [2]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Methylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Colon-26 carcinoma cells; Skin; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a histone methyltransferase EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of histone methylation induced under hypoxic tumor microenvironment.

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [2]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Methylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: B16-BL6 cells; Skin; Homo sapiens (Human); CVCL_0157
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a histone methyltransferase EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of histone methylation induced under hypoxic tumor microenvironment.

Unspecified malignant neoplasms of unspecified sites [ICD-11: 2D4Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [2]

• Sensitive Disease: cancer [ICD-11: 2D4Z]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: B16 cells; Skin; Homo sapiens (Human); CVCL_F936
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: The?protein expression?of the?enhancer of zeste homolog 2?(EZH2),?histone methyltransferase?and its target?histone H3?trimethylation at lysine 27 (H3K27Me3) level increased under hypoxia. The induction of H3K27Me3 under hypoxia was suppressed by EZH2?siRNA?and 3-deazaneplanocin A (DZNep), an EZH2 inhibitor. Furthermore, both EZH2?siRNA?and DZNep significantly reduced the?cell viability?after SN-38 treatment and improved the chemoresistance to SN-38 under hypoxia. These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a?histone methyltransferase?EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of?histone methylation?induced under hypoxic?tumor microenvironment.

Key Molecule: Histone H3 lysine 27 trimethylation (H3K27me3) [2]

• Sensitive Disease: cancer [ICD-11: 2D4Z]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: B16 cells; Skin; Homo sapiens (Human); CVCL_F936
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: The?protein expression?of the?enhancer of zeste homolog 2?(EZH2),?histone methyltransferase?and its target?histone H3?trimethylation at lysine 27 (H3K27Me3) level increased under hypoxia. The induction of H3K27Me3 under hypoxia was suppressed by EZH2?siRNA?and 3-deazaneplanocin A (DZNep), an EZH2 inhibitor. Furthermore, both EZH2?siRNA?and DZNep significantly reduced the?cell viability?after SN-38 treatment and improved the chemoresistance to SN-38 under hypoxia. These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a?histone methyltransferase?EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of?histone methylation?induced under hypoxic?tumor microenvironment.

References

• Ref 1: HDAC1,2 inhibition impairs EZH2- and BBAP-mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphomaOncotarget. 2015 Mar 10;6(7):4863-87. doi: 10.18632/oncotarget.3120.
• Ref 2: 3-deazaneplanocin A, a histone methyltransferase inhibitor, improved the chemoresistance induced under hypoxia in melanoma cells. Biochem Biophys Res Commun. 2023 Oct 15;677:26-30.