Drug Information

Drug (ID: DG01831) and It's Reported Resistant Information

• Name: Afeletecan
• Synonyms: Afeletecan; Afeletecan free base; UNII-IX0QAD6RD2; IX0QAD6RD2; 215604-75-4; (S)-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl ((4-(((2R,3S,4R,5R,6S)-3,5-dihydroxy-4-methoxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)phenyl)carbamothioyl)-L-histidyl-L-valinate; Afeletecan [INN]; CHEMBL2105857; Q27280930; [(19S)-19-ethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaen-19-yl] (2S)-2-[[(2S)-2-[[4-[(2R,3S,4R,5R,6S)-3,5-dihydroxy-4-methoxy-6-methyloxan-2-yl]oxyphenyl]carbamothioylamino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoate; Camptothecin, ester with N-((p-((3-O-methyl-beta-L-fucopyranosyl)oxy)phenyl)thiocarbamoyl)-L-histidyl-L-valine
• Indication:
  In total 1 Indication(s)
  Breast cancer [ICD-11: 2C60]; Phase 1; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Colorectal cancer [ICD-11: 2B91]; [1]
• Target: DNA topoisomerase I (TOP1); TOP1_HUMAN; [1]
• Formula: 14
• IsoSMILES: CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=CC5=CC=CC=C5N=C4C3=C2)OC(=O)[C@H](C(C)C)NC(=O)[C@H](CC6=CN=CN6)NC(=S)NC7=CC=C(C=C7)O[C@@H]8[C@H]([C@@H]([C@@H]([C@@H](O8)C)O)OC)O
• InChI: InChI=1S/C45H49N7O11S/c1-6-45(30-17-33-35-25(15-24-9-7-8-10-31(24)49-35)19-52(33)40(56)29(30)20-60-43(45)58)63-41(57)34(22(2)3)51-39(55)32(16-27-18-46-21-47-27)50-44(64)48-26-11-13-28(14-12-26)62-42-37(54)38(59-5)36(53)23(4)61-42/h7-15,17-18,21-23,32,34,36-38,42,53-54H,6,16,19-20H2,1-5H3,(H,46,47)(H,51,55)(H2,48,50,64)/t23-,32-,34-,36+,37-,38+,42+,45-/m0/s1
• InChIKey: SLOJCSGNHWIKIG-JNYZSSQASA-N
• PubChem CID: 9941008
• TTD Drug ID: D07PMG

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Colorectal cancer [ICD-11: 2B91]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA (RAMS11) [1]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: CCD18-Co cells; Colon; Homo sapiens (Human); CVCL_2379
• In Vivo Model: NOD/SCID mice model; Mus musculus
• Experiment for Molecule Alteration: Knockdown assay; Overexpression assay; qRT-PCR; Western bloting analysis; RNA-seq; RIP experiments assay; ChIP assay; RNA pull down assay
• Experiment for Drug Resistance: Soft agar assay
• Mechanism Description: Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2alpha supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC.

References

• Ref 1: Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progressionNat Commun. 2020 May 1;11(1):2156. doi: 10.1038/s41467-020-15547-8.