Drug Information

Drug (ID: DG00789) and It's Reported Resistant Information

• Name: Pamidronate
• Synonyms: PAMIDRONIC ACID; pamidronate; 40391-99-9; Aredia; Amidronate; Aminomux; (3-amino-1-hydroxy-1-phosphonopropyl)phosphonic acid; Acide pamidronique [INN-French]; Acido pamidronico [INN-Spanish]; Acidum pamidronicum [INN-Latin]; PAMIDRONATE DISODIUM; (3-amino-1-hydroxypropane-1,1-diyl)bis(phosphonic acid); Disodium pamidronate; UNII-OYY3447OMC; (3-Amino-1-hydroxypropylidene)diphosphonic acid; CHEMBL834; OYY3447OMC; Phosphonic acid, (3-amino-1-hydroxypropylidene)bis-; (3-AMINO-1-HYDROXY-1-PHOSPHONO-PROPYL)PHOSPHONIC ACID; 3-amino-1-hydroxypropane-1,1-diphosphonic acid; CGP-23339AE; NCGC00159433-02; DSSTox_CID_3414; Acido pamidronico; Acide pamidronique; Acidum pamidronicum; DSSTox_RID_77017; DSSTox_GSID_23414; 1159812-33-5; (3-Amino-1-hydroxypropane-1,1-diyl)diphosphonic acid; Pamidronic acid [INN:BAN]; Ribodroat; 57248-88-1; Bisphosphonate 6; Ribodroat (TN); CAS-40391-99-9; (3-Amino-1-hydroxypropylidene)bisphosphonic acid; C3H11NO7P2; Pamidronic acid (INN); EINECS 254-905-2; starbld0044121; ChemDiv1_025240; 3-Amino-1-hydroxypropylidene-1,1-diphosphonate; SCHEMBL18361; BIDD:GT0538; CHEBI:7903; GTPL7259; JMC515594 Compound 62; DTXSID4023414; BDBM12581; HMS658L06; HMS2090C13; HMS3749A11; BCP17709; CCG-2075; HY-B0012; ZINC3812862; Tox21_111664; 2631AH; HSCI1_000312; MFCD00168777; s2063; STL510914; AKOS003599275; Tox21_111664_1; CS-7787; DB00282; MCULE-4373491291; NCGC00159433-03; NCGC00165862-02; DB-049579; FT-0630610; C07395; C75045; D07281; 391P999; A825084; Propane-1-hydroxy-3-amino-1,1-diphosphonic acid; Q627499; SR-01000514873; 3-amino-1-hydroxypropane-1,1-diyldiphosphonic acid; SR-01000514873-1; (3-Amino-1-hydroxy-1-phosphono-propyl)-phosphonic acid; Phosphonic acid, P,P'-(3-amino-1-hydroxypropylidene)bis-
• Indication:
  In total 1 Indication(s)
  Hypercalcaemia [ICD-11: 5B91]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
• Target: Geranyltranstransferase (FDPS); FPPS_HUMAN; [1]
• Formula: C3H11NO7P2
• IsoSMILES: C(CN)C(O)(P(=O)(O)O)P(=O)(O)O
• InChI: 1S/C3H11NO7P2/c4-2-1-3(5,12(6,7)8)13(9,10)11/h5H,1-2,4H2,(H2,6,7,8)(H2,9,10,11)
• InChIKey: WRUUGTRCQOWXEG-UHFFFAOYSA-N
• PubChem CID: 4674
• ChEBI ID: CHEBI:7903
• TTD Drug ID: D0BF8G

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

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: U266 cells; Bone marrow; Homo sapiens (Human); CVCL_0566
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: Pseudomonas aeruginosa strain B-730P/17; 287
• Experiment for Drug Resistance: CellTiter 96 one solution proliferation assay
• Mechanism Description: In response to pamidronate, there was significant inhibition of cell proliferation in MDA-231 and SKBR-3 cells, compared to MDA-175 cells. This correlated with their respective basal levels of N-ras and H-ras. N-ras and H-ras protein levels were both reduced in MDA-231 cells, and to lesser extent in SKBR-3 cells, following exposure to pamidronate, whereas these markers were not altered in MDA-175 cells, resistance to pamidronate may result from low levels of GTPase-activating proteins, such as N-ras and H-ras, in tumor cells.

Key Molecule: GTPase Nras (NRAS) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: U266 cells; Bone marrow; Homo sapiens (Human); CVCL_0566
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: Pseudomonas aeruginosa strain B-730P/17; 287
• Experiment for Drug Resistance: CellTiter 96 one solution proliferation assay
• Mechanism Description: In response to pamidronate, there was significant inhibition of cell proliferation in MDA-231 and SKBR-3 cells, compared to MDA-175 cells. This correlated with their respective basal levels of N-ras and H-ras. N-ras and H-ras protein levels were both reduced in MDA-231 cells, and to lesser extent in SKBR-3 cells, following exposure to pamidronate, whereas these markers were not altered in MDA-175 cells, resistance to pamidronate may result from low levels of GTPase-activating proteins, such as N-ras and H-ras, in tumor cells.

References

• Ref 1: Pamidronate resistance and associated low ras levels in breast cancer cells: a role for combinatorial therapy .Ann Clin Lab Sci. 2004 Summer;34(3):263-70.