Mipsagargin

DRACPC ID  DRACPC0069

Active Ingredients   Mipsagargin

Description  A soluble, thapsigargin prodrug containing the cytotoxic analog of thapsigargin, 8-O-(12Aminododecanoyl)-8-O debutanoylthapsigargin (12-ADT) linked, via a carboxyl group, to the targeting peptide containing aspartic acid with potential antineoplastic activity. Upon intravenous administration, mipsagargin targets prostate specific membrane antigen (PSMA), a type II membrane carboxypeptidase, which is overexpressed in prostate cancer cells and in the neovasculature of most solid tumors but not in normal blood vessels. Mipsagargin is subsequently converted, through hydrolysis, into the active cytotoxic analog of thapsigargin 12-ADT-Asp. 12-ADT binds to and blocks the Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase (SERCA) pump, thereby increasing the concentration of cytosolic calcium which leads to an induction of apoptosis. By preventing nutrient supply to tumor cells, G-202 may be able to inhibit tumor growth. Compared to thapsigargin alone, thapsigargin prodrug G-202 is able to achieve higher concentrations of the active agents at the tumor site while avoiding systemic toxicity.

Synonyms  G-202; Mipsagargin

Type  Small Molecule

Disease  Prostate Cancer, Advanced Solid Tumors, Glioblastoma Multiforme, Hepatocellular Carcinoma

Classification

  

Peptide and derivative

Structure Information


Molecular Formula  C66H100N6O27

Molecular Weight  1409.5

Active Sequence  XXXXE

Sequence Length  5

Modification  X(1)=Asn(Unk), X(2/3/4)=gGlu

Structure

 

Show IUPAC/InChI/SMILES

IUPAC Name  (2S)-2-[[(4S)-4-[[(4S)-4-[[(4S)-4-[[(2S)-4-[[12-[[(3S,3aR,4S,6S,6aR,7S,8S,9bS)-6-acetyloxy-3,3a-dihydroxy-3,6,9-trimethyl-8-[(Z)-2-methylbut-2-enoyl]oxy-7-octanoyloxy-2-oxo-4,5,6a,7,8,9b-hexahydroazuleno[4,5-b]furan-4-yl]oxy]-12-oxododecyl]amino]-2-amino-4-oxobutanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]pentanedioic acid

InChI  InChI=1S/C66H100N6O27/c1-8-10-11-17-20-24-51(81)96-55-53-52(37(4)54(55)97-62(91)36(3)9-2)56-66(94,65(7,93)63(92)98-56)44(35-64(53,6)99-38(5)73)95-50(80)23-21-18-15-13-12-14-16-19-22-33-68-48(77)34-39(67)57(82)72-43(61(89)90)27-31-47(76)70-41(59(85)86)25-29-45(74)69-40(58(83)84)26-30-46(75)71-42(60(87)88)28-32-49(78)79/h9,39-44,53-56,93-94H,8,10-35,67H2,1-7H3,(H,68,77)(H,69,74)(H,70,76)(H,71,75)(H,72,82)(H,78,79)(H,83,84)(H,85,86)(H,87,88)(H,89,90)/b36-9-/t39-,40-,41-,42-,43-,44-,53+,54-,55-,56-,64-,65+,66+/m0/s1

InChI_Key UPYNTAIBQVNPIH-ODMLWHIESA-N

SMILES  C/C=C(C(O[C@H]1C(C)=C2[C@@H]3OC([C@@](O)([C@@]([C@H](C[C@](OC(C)=O)([C@H]2[C@@H]1OC(CCCCCCC)=O)C)OC(CCCCCCCCCCCNC(C[C@@H](C(N[C@H](C(O)=O)CCC(N[C@H](C(O)=O)CCC(N[C@H](C(O)=O)CCC(N[C@H](C(O)=O)CCC(O)=O)=O)=O)=O)=O)N)=O)=O)3O)C)=O)=O)/C

External Codes


PubChem CID  24772106

DrugBank Accession Number  DB11813

NCI Thesaurus Code  C90554  

UNII  Q032I35QMX   GSRS

CAS  1245732-48-2



Drug approval


Drug indication
    Mipsagargin has been used in trials studying the treatment of Prostate Cancer, Prostatic Neoplasms, Advanced Solid Tumors, Glioblastoma Multiforme, and Hepatocellular Carcinoma, among others.

    The drug is not approved.

ClinicalTrials.gov Identifier Title Condition or disease Phase Purpose
NCT01777594 A Phase II, Multicenter, Single-Arm Study of G-202 (Mipsagargin) as Second-Line Therapy Following Sorafenib for Adult Patients With Progressive Advanced Hepatocellular Carcinoma Advanced Adult Hepatocellular Carcinoma Phase 2 Treatment
NCT02067156 An Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy, Safety and CNS Exposure of G-202 (Mipsagargin) in Patients With Recurrent or Progressive Glioblastoma Glioblastoma Multiforme Phase 2 Treatment
NCT01056029 An Open Label, Single-Arm, Dose-Escalation Phase 1 Study of G-202 (Mipsagargin) in Patients With Advanced Solid Tumors Advanced Solid Tumors Phase 1 Treatment
NCT02607553 G-202-006: An Open-Label, Single-Arm, Phase II Study to Evaluate the Safety and Activity of G-202 in Patients With Clear Cell Renal Cell Carcinoma That Expresses PSMA Clear Cell Renal Cell Carcinoma Phase 2 Treatment
NCT02381236 G-202-005: An Open-Label, Single-Arm, Phase II Study to Evaluate the Safety and Activity of G-202 Administered in the Neoadjuvant Setting Followed by Radical Prostatectomy in Patients With Adenocarcinoma of the Prostate Prostatic Neoplasms Phase 2 Treatment

    More clinical information is obtained from ClinicalTrials.gov.





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