Drug Information

Drug (ID: DG01191) and It's Reported Resistant Information

• Name: Cabazitaxel
• Synonyms: CABAZITAXEL; 183133-96-2; Jevtana; Taxoid XRP6258; Cabazitaxelum; TXD 258; Xrp6258; XRP-6258; UNII-51F690397J; XRP 6258; Jevtana (TN); CHEBI:63584; NSC-761432; 51F690397J; kabazitaxel; Jevtana Kit; Cabazitaxel (Jevtana); (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-3-phenylpropanoyl)oxy)-11-hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate.; cabazitaxel acetonate; Cabazitaxel Injection; Cabazitaxel [USAN:INN]; Jevanta; TXD258; RPR 116258A; RPR-116258A; Cabazitaxel (USAN/INN); SCHEMBL179674; GTPL6798; CHEMBL1201748; AMY4317; DTXSID40171389; EX-A838; TXD-258; C45H57NO14; MFCD18827611; NSC761432; NSC794609; s3022; ZINC85536932; AKOS032947285; CCG-270519; CS-0972; DB06772; NSC 761432; NSC-794609; NCGC00346704-01; NCGC00346704-03; AS-75355; HY-15459; X7252; A25044; D09755; AB01273971-01; AB01273971_02; Q412963; SR-01000941585; J-011721; J-519981; SR-01000941585-1; (((tertbutoxy)carbonyl)amino)-2-hydroxy-3-phenylpropanoate1-hydroxy-7beta,10beta-dimethoxy-9-oxo-5beta,20-epoxytax-11-ene-2alpha,4,13alpha-triyl 4-acetate 2-benzoate 13-((2R,3S)-3-; (1S)-5beta,20-Epoxy-9-oxo-7beta,10beta-dimethoxytaxa-11-ene-1,2alpha,4alpha,13alpha-tetraol 2-benzoate 4-acetate 13-[(2R,3S)-2-hydroxy-3-(tert-butoxycarbonylamino)-3-phenylpropionate]; (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetyloxy)-15-{[(2R,3S)-3-{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoyl]oxy}-1-hydroxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3),(1) .0 , ]heptadec-13-en-2-yl benzoate; (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetyloxy)-15-{[(2R,3S)-3-{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoyl]oxy}-1-hydroxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate; (2alpha,5beta,7beta,10beta,13alpha)-4-acetoxy-13-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl}oxy)-1-hydroxy-7,10-dimethoxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate; (2AR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-3-phenylpropanoyl)oxy)-11-hydroxy-4,6-dimethoxy-4a,8,13,1; (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-3-phenylpropanoyl)oxy)-11-hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate; [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1-hydroxy-15-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]oxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate; 1-hydroxy-7,10-dimethoxy-9-oxo-5,20-epoxytax-11-ene-2,4,13-triyl 4-acetate 2-benzoate 13-((2R,3S)-3-(((tertbutoxy)carbonyl)amino)-2-hydroxy-3-phenylpropanoate); 1-hydroxy-7 ,10 -dimethoxy-9-oxo-5 ,20-epoxytax-11-ene-2 ,4,13 -triyl 4-acetate 2-benzoate 13-[(2R,3S)-3-{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoate]; Benzenepropanoic acid, beta-[[(1,1-dimethylethoxy)carbonyl]amino]-alpha-hydroxy-, (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-11-hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester, (alphaR,betaS)-
• Indication:
  In total 2 Indication(s)
  Breast cancer [ICD-11: 2C60]; Approved; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Prostate cancer [ICD-11: 2C82]; [1]
• Target: Tubulin (TUB); NOUNIPROTAC; [1]
• Formula: C45H57NO14
• IsoSMILES: CC1=C2[C@H](C(=O)[C@@]3([C@H](C[C@@H]4[C@]([C@H]3[C@@H]([C@@](C2(C)C)(C[C@@H]1OC(=O)[C@@H]([C@H](C5=CC=CC=C5)NC(=O)OC(C)(C)C)O)O)OC(=O)C6=CC=CC=C6)(CO4)OC(=O)C)OC)C)OC
• InChI: 1S/C45H57NO14/c1-24-28(57-39(51)33(48)32(26-17-13-11-14-18-26)46-40(52)60-41(3,4)5)22-45(53)37(58-38(50)27-19-15-12-16-20-27)35-43(8,36(49)34(55-10)31(24)42(45,6)7)29(54-9)21-30-44(35,23-56-30)59-25(2)47/h11-20,28-30,32-35,37,48,53H,21-23H2,1-10H3,(H,46,52)/t28-,29-,30+,32-,33+,34+,35-,37-,43+,44-,45+/m0/s1
• InChIKey: BMQGVNUXMIRLCK-OAGWZNDDSA-N
• PubChem CID: 9854073
• ChEBI ID: CHEBI:63584
• TTD Drug ID: D02HSB
• INTEDE ID: DR0252
• DrugBank ID: DB06772

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Prostate cancer [ICD-11: 2C82]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tubulin beta-3 chain (TUBB3) [1]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Prostate cancer [ICD-11: 2C82]
• The Specified Disease: Prostate cancer
• The Studied Tissue: Prostate
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.82E-01; Fold-change: 2.20E-02; Z-score: 1.10E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• In Vitro Model: HuTu80 cells; Small intestine; Homo sapiens (Human); CVCL_1301
• In Vitro Model: DU145-DR cells; Brain; Homo sapiens (Human); CVCL_4Y36
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression.

Key Molecule: Phosphatase and tensin homolog (PTEN) [1]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• In Vitro Model: HuTu80 cells; Small intestine; Homo sapiens (Human); CVCL_1301
• In Vitro Model: DU145-DR cells; Brain; Homo sapiens (Human); CVCL_4Y36
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression.

Key Molecule: Mitogen-activated protein kinase 1 (MAPK1) [2]

• Resistant 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
• 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.

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

• Resistant 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
• 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.

Key Molecule: Eukaryotic elongation factor 2 kinase (eEF2K) [2]

• Resistant 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
• 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.

Key Molecule: Guanine nucleotide-binding protein G(i) subunit alpha-2 (GNAI2) [2]

• Resistant 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
• 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.

Key Molecule: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 (PLCB3) [2]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Up-regulation
• Cell Pathway Regulation: Oxytocin signaling pathway; Activation; hsa04921
• Experiment for Molecule Alteration: Gene expression analysis
• 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.

Key Molecule: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 (PLCB3) [2]

• Resistant 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
• 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.

Key Molecule: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) [2]

• Resistant 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
• 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.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphatase and tensin homolog (PTEN) [1]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Prostate cancer [ICD-11: 2C82]
• The Specified Disease: Prostate cancer
• The Studied Tissue: Prostate
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.27E-02; Fold-change: 1.09E-01; Z-score: 2.44E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• In Vitro Model: HuTu80 cells; Small intestine; Homo sapiens (Human); CVCL_1301
• In Vitro Model: DU145-DR cells; Brain; Homo sapiens (Human); CVCL_4Y36
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression.

Key Molecule: Tubulin beta-3 chain (TUBB3) [1]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• In Vitro Model: HuTu80 cells; Small intestine; Homo sapiens (Human); CVCL_1301
• In Vitro Model: DU145-DR cells; Brain; Homo sapiens (Human); CVCL_4Y36
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression.

References

• Ref 1: TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer .Int J Mol Sci. 2019 Aug 13;20(16):3936. doi: 10.3390/ijms20163936. 10.3390/ijms20163936
• 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.