Drug Information

Drug (ID: DG00636) and It's Reported Resistant Information

• Name: Pingyangmycin
• Synonyms: Pingyangmycin; Bleomycetin; Bleomycinamide, N1-[3-[(4-aminobutyl)amino]propyl]-; (Bleomycin A5); CHEMBL2002141; BCP23597; NSC350895; NSC-350895; Q2095702; Bleomycinamide, N(1)-[3-[(4-aminobutyl)amino]propyl]-
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Tongue squamous cell carcinoma [ICD-11: 2B62]; [1]
  Salivary gland carcinoma [ICD-11: 2E60]; [2]
• Formula: C57H89N19O21S2
• IsoSMILES: CC1=C(N=C(N=C1N)C(CC(=O)N)NCC(C(=O)N)N)C(=O)NC(C(C2=CN=CN2)OC3C(C(C(C(O3)CO)O)O)OC4C(C(C(C(O4)CO)O)OC(=O)N)O)C(=O)NC(C)C(C(C)C(=O)NC(C(C)O)C(=O)NCCC5=NC(=CS5)C6=NC(=CS6)C(=O)NCCCNCCCCN)O
• InChI: 1S/C57H89N19O21S2/c1-22-35(73-48(76-46(22)61)27(14-33(60)80)68-15-26(59)47(62)86)52(90)75-37(43(28-16-65-21-69-28)95-56-45(41(84)39(82)31(17-77)94-56)96-55-42(85)44(97-57(63)92)40(83)32(18-78)93-55)53(91)70-24(3)38(81)23(2)49(87)74-36(25(4)79)51(89)67-13-8-34-71-30(20-98-34)54-72-29(19-99-54)50(88)66-12-7-11-64-10-6-5-9-58/h16,19-21,23-27,31-32,36-45,55-56,64,68,77-79,81-85H,5-15,17-18,58-59H2,1-4H3,(H2,60,80)(H2,62,86)(H2,63,92)(H,65,69)(H,66,88)(H,67,89)(H,70,91)(H,74,87)(H,75,90)(H2,61,73,76)
• InChIKey: QYOAUOAXCQAEMW-UHFFFAOYSA-N
• PubChem CID: 84046
• DrugBank ID: DB12992

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

Tongue cancer [ICD-11: 2B62]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-21 [1]

• Resistant Disease: Tongue squamous cell carcinoma [ICD-11: 2B62.0]
• Molecule Alteration: Expression; Overexpression
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MYCN/miR-21/CADM1 pathway; Regulation; N.A.
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• Experiment for Molecule Alteration: qRT-PCR; Western blot; Co-immunoprecipitation; Luciferase reporter assay; ChIP assay; miRNA in situ hybridization assay; Immunohistochemistry
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: We found that miR-21 directly targeted CADM1 expression, which was downregulated in drug-resistant TC cells. Restored CADM1 expression sensitized TC cells to chemotherapy, but CADM1 knockdown induced chemo-resistance. Mechanically, CADM1 interacted with BMI1 to inhibit its nuclear translocation. Moreover, MYCN which was overexpressed in drug-resistant TC cells directly bound to the miR-21 promoter to upregulated miR-21 expression in TC cells. Importantly, the expression levels of miR-21 and CADM1 negatively correlated, but MYCN and miR-21 positively correlated in TC tissues.

Salivary gland carcinoma [ICD-11: 2E60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Prominin-1 (PROM1) [2]

• Resistant Disease: Salivary gland adenoid cystic carcinoma [ICD-11: 2E60.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MET/PI3K/AKT/mTOR signaling pathway; Activation; hsa04150
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: KOA-1 cells; Skin; Homo sapiens (Human); CVCL_L997
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: CD133 activates the PI3K/AKT, AKT/Wnt and other signaling pathways and affects the behavior of CD133+ cells, thereby playing a major role in cancer therapy. In addition, CD133 is also involved in the regulation of tumor resistance. Long-term chemotherapy leads to a significant increase in CD133 expression. Targeting CD133 can reverse drug resistance in colorectal cancer via the AKT/NF-kappa-B/multidrug resistance protein (MDR)1 pathway.

References

• Ref 1: Intermittent High-Dose Scheduling of AZD8835, a Novel Selective Inhibitor of PI3KAlpha and PI3K Delta, Demonstrates Treatment Strategies for PIK3CA-Dependent Breast CancersMol Cancer Ther. 2016 May;15(5):877-89. doi: 10.1158/1535-7163.MCT-15-0687. Epub 2016 Feb 2.
• Ref 2: Effects of CD133 expression on chemotherapy and drug sensitivity of adenoid cystic carcinoma .Mol Med Rep. 2022 Jan;25(1):18. doi: 10.3892/mmr.2021.12534. Epub 2021 Nov 18. 10.3892/mmr.2021.12534