Drug Information

Drug (ID: DG00718) and It's Reported Resistant Information

• Name: Cloperastine
• Synonyms: Cloperastine; 3703-76-2; 1-(2-((4-chlorophenyl)(phenyl)methoxy)ethyl)piperidine; Cloperastine [INN]; 1-[2-[(4-chlorophenyl)-phenylmethoxy]ethyl]piperidine; HT-11; Piperidine, 1-[2-[(4-chlorophenyl)phenylmethoxy]ethyl]-; Cloperastine (hydrochloride); Cloperastine (INN); Cloperastina; Cloperastinum; Cloperastinum [INN-Latin]; Cloperastina [INN-Spanish]; NSC-758635; HT 11; EINECS 223-042-3; 1-{2-[(4-chlorophenyl)(phenyl)methoxy]ethyl}piperidine; BRN 0275589; 1-(2-((4-Chlorophenyl)phenylmethoxy)ethyl)piperidine; cloperastine-fendizoate; Spectrum_001570; Prestwick0_000793; Prestwick1_000793; Prestwick2_000793; Prestwick3_000793; Spectrum2_001596; Spectrum3_001895; Spectrum4_000844; Spectrum5_001448; BSPBio_000926; BSPBio_003430; KBioGR_001447; KBioSS_002050; 5-20-02-00105 (Beilstein Handbook Reference); DivK1c_000840; SCHEMBL284715; SPBio_001592; SPBio_002865; BPBio1_001020; CHEMBL415087; 1- 2-((p-Chloro-alpha-phenylbenzyl)oxy)ethyl piperidine; 1-{2-((p-Chloro-alpha-phenylbenzyl)oxy)ethyl}piperidine; DTXSID7048532; CHEBI:94448; KBio1_000840; KBio2_002050; KBio2_004618; KBio2_007186; KBio3_002933; NINDS_000840; Piperidine, 1-(2-((p-chloro-alpha-phenylbenzyl)oxy)ethyl)-; BDBM50237287; STK646871; AKOS005577799; DB09002; NSC 758635; IDI1_000840; NCGC00178069-01; NCGC00178069-02; NCGC00178069-03; M201; SBI-0051861.P002; AB00053681; FT-0746924; VU0244436-2; D03557; AB00053681_08; Q2055825; BRD-A80908310-003-05-4; BRD-A80908310-003-08-8; 1-[2-[(4-chlorophenyl)-phenyl-methoxy]ethyl]piperidine; 1-(2-[(4-Chlorophenyl)(phenyl)methoxy]ethyl)piperidine #; 1-(2-[(p-Chloro-.alpha.-phenylbenzyl)oxy]ethyl)piperidine; Piperidine, 1-(2-((p-chloro-.alpha.-phenylbenzyl)oxy)ethyl)-; Piperidine, 1-(2-((4-chlorophenyl)phenylmethoxy)ethyl)- (9CI); Piperidine, 1-[2-[(4-chlorophenyl)phenylmethoxy]ethyl]-, hydrochloride
• Indication:
  In total 1 Indication(s)
  Cough [ICD-11: MD12]; Approved; [1]
• Formula: C20H24ClNO
• IsoSMILES: C1CCN(CC1)CCOC(C2=CC=CC=C2)C3=CC=C(C=C3)Cl
• InChI: 1S/C20H24ClNO/c21-19-11-9-18(10-12-19)20(17-7-3-1-4-8-17)23-16-15-22-13-5-2-6-14-22/h1,3-4,7-12,20H,2,5-6,13-16H2
• InChIKey: FLNXBVJLPJNOSI-UHFFFAOYSA-N
• PubChem CID: 2805
• ChEBI ID: CHEBI:94448
• TTD Drug ID: D0O8IS
• DrugBank ID: DB09002

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Cervical cancer [ICD-11: 2C77]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Histamine receptor H1 (HRH1) [1]

• Sensitive Disease: Cervical cancer [ICD-11: 2C77.0]
• Molecule Alteration: Function; Inhibition
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• Experiment for Molecule Alteration: Quantitative RT-PCR assay
• Experiment for Drug Resistance: CCK-8 assay; Flow cytometric analysis
• Mechanism Description: Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells. Here we show that cloperastine and two other histamine H1 receptor antagonists selectively kill HeLa cisR cells at concentrations that little affect parental HeLa S cells.

Prostate cancer [ICD-11: 2C82]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D) [2]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Phosphorylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Oxytocin signaling pathway; Activation; hsa04921
• In Vitro Model: DU145CR cells; prostate; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: MS analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.

References

• Ref 1: Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells .Sci Rep. 2021 Jan 15;11(1):1492. doi: 10.1038/s41598-021-81077-y. 10.1038/s41598-021-81077-y
• Ref 2: G-protein signaling of oxytocin receptor as a potential target for cabazitaxel-resistant prostate cancer. PNAS Nexus. 2024 Jan 4;3(1):pgae002.