Drug Information

Drug (ID: DG00363) and It's Reported Resistant Information

• Name: Cevipabulin
• Synonyms: Cevipabulin; 849550-05-6; UNII-P14M0DWS2J; TTI-237; P14M0DWS2J; 849550-05-6 (free base); 5-Chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-((1S)-2,2,2-trifluoro-1-methylethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine; 5-chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(1S)-2,2,2-trifluoro-1- methylethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine.; 5-chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine; Cevipabulin [INN]; TTI 237; 5-chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine; Cevipabulin(TTI 237); SCHEMBL4042827; CHEMBL1182714; AOB5715; DTXSID00233997; EX-A607; BCP28162; MFCD09832720; ZINC13981125; CS-4196; DB12533; HY-14949; B5922; A12591; 550C056; J-690362; Q27285989; TTI 237; TTI-237; TTI237; D06576; D 06576; D-06576; (S)-5-Chloro-6-(2,6-difluoro-4-(3-(methylamino)propoxy)phenyl)-N-(1,1,1-trifluoropropan-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine; 5-chloro-6-{2,6-difluoro-4-[3-(methylamino) propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine; 5-chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine; 5-chloro-6{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (4 diseases)
  Brain cancer [ICD-11: 2A00]; [1]
  Cervical cancer [ICD-11: 2C77]; [1]
  Colorectal cancer [ICD-11: 2B91]; [1]
  Oral squamous cell carcinoma [ICD-11: 2B6E]; [1]
• Formula: C18H18ClF5N6O
• IsoSMILES: C[C@@H](C(F)(F)F)NC1=C(C(=NC2=NC=NN12)Cl)C3=C(C=C(C=C3F)OCCCNC)F
• InChI: 1S/C18H18ClF5N6O/c1-9(18(22,23)24)28-16-14(15(19)29-17-26-8-27-30(16)17)13-11(20)6-10(7-12(13)21)31-5-3-4-25-2/h6-9,25,28H,3-5H2,1-2H3/t9-/m0/s1
• InChIKey: ZUZPCOQWSYNWLU-VIFPVBQESA-N
• PubChem CID: 11488110
• DrugBank ID: DB12533

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Brain cancer [ICD-11: 2A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Glioma [ICD-11: 2A00.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

Oral squamous cell carcinoma [ICD-11: 2B6E]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• In Vitro Model: KB-8-5 cells; Mouth; Homo sapiens (Human); CVCL_5994
• In Vitro Model: KB-V1 cells; Mouth; Homo sapiens (Human); CVCL_2089
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

Colorectal cancer [ICD-11: 2B91]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Colorectal carcinoma [ICD-11: 2B91.3]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

Cervical cancer [ICD-11: 2C77]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Cervical carcinoma [ICD-11: 2C77.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

References

• Ref 1: TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008 Apr 1;68(7):2292-300. doi: 10.1158/0008-5472.CAN-07-1420.