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Details

Stereochemistry ABSOLUTE
Molecular Formula C51H88O60S13
Molecular Weight 2078.053
Optical Activity UNSPECIFIED
Defined Stereocenters 29 / 29
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PIXATIMOD

SMILES

[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])C[C@H](CC[C@]4(C)[C@@]3([H])CC[C@]12C)O[C@]5([H])O[C@H](COS(O)(=O)=O)[C@@H](O[C@@]6([H])O[C@H](COS(O)(=O)=O)[C@@H](O[C@@]7([H])O[C@H](COS(O)(=O)=O)[C@@H](O[C@@]8([H])O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]8OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]7OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]6OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]5OS(O)(=O)=O)[C@H](C)CCCC(C)C

InChI

InChIKey=LNUFLCYMSVYYNW-ZPJMAFJPSA-N
InChI=1S/C51H88O60S13/c1-22(2)7-6-8-23(3)27-11-12-28-26-10-9-24-17-25(13-15-50(24,4)29(26)14-16-51(27,28)5)95-46-42(108-121(79,80)81)38(104-117(67,68)69)34(30(96-46)18-91-112(52,53)54)100-47-43(109-122(82,83)84)39(105-118(70,71)72)35(31(97-47)19-92-113(55,56)57)101-48-44(110-123(85,86)87)40(106-119(73,74)75)36(32(98-48)20-93-114(58,59)60)102-49-45(111-124(88,89)90)41(107-120(76,77)78)37(103-116(64,65)66)33(99-49)21-94-115(61,62)63/h22-49H,6-21H2,1-5H3,(H,52,53,54)(H,55,56,57)(H,58,59,60)(H,61,62,63)(H,64,65,66)(H,67,68,69)(H,70,71,72)(H,73,74,75)(H,76,77,78)(H,79,80,81)(H,82,83,84)(H,85,86,87)(H,88,89,90)/t23-,24+,25+,26+,27-,28+,29+,30-,31-,32-,33-,34-,35-,36-,37-,38+,39+,40+,41+,42-,43-,44-,45-,46-,47-,48-,49-,50+,51-/m1/s1

HIDE SMILES / InChI

Molecular Formula C51H88O60S13
Molecular Weight 2078.053
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 29 / 29
E/Z Centers 0
Optical Activity UNSPECIFIED

PG-545 is a heparan sulfate (HS) mimetic that inhibits tumour angiogenesis by sequestering angiogenic growth factors in the extracellular matrix (ECM), thus limiting subsequent binding to receptors. Importantly, PG-545 also inhibits heparanase, the only endoglycosidase which cleaves HS chains in the ECM. The anti- respiratory syncytial virus (RSV) activity of PG-545 was due to both partial inhibition of the virus attachment to cells and a more profound interference with some post-attachment steps as PG-545 efficiently neutralized infectivity of the cell-adsorbed virus. The anti-RSV activity of PG-545 was reduced when tested in the presence of human nasal secretions. Serial passages of RSV in the presence of increasing concentrations of PG-545 selected for weakly resistant viral variants that comprised the F168S and the P180S amino acid substitutions in the viral G protein. PG-545 has an immunomodulatory properties. PG-545 stimulates innate immune responses against tumours in preclinical cancer models. PG-545 is in phase I clinical trial for the treatment of pancreatic cancer.

Approval Year

PubMed

PubMed

TitleDatePubMed
PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models.
2011 Feb 15
Potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate.
2012 Jan
The heparan sulfate mimetic PG545 interferes with Wnt/β-catenin signaling and significantly suppresses pancreatic tumorigenesis alone and in combination with gemcitabine.
2015 Mar 10
PG545 enhances anti-cancer activity of chemotherapy in ovarian models and increases surrogate biomarkers such as VEGF in preclinical and clinical plasma samples.
2015 May
The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles.
2016 Feb
Heparan sulfate mimetic PG545-mediated antilymphoma effects require TLR9-dependent NK cell activation.
2016 Jan
Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis.
2016 Jan 19
Heparanase Inhibition Reduces Glucose Levels, Blood Pressure, and Oxidative Stress in Apolipoprotein E Knockout Mice.
2017
Inhibition of Heparanase in Pediatric Brain Tumor Cells Attenuates their Proliferation, Invasive Capacity, and In Vivo Tumor Growth.
2017 Aug
The Heparanase Inhibitor PG545 Attenuates Colon Cancer Initiation and Growth, Associating with Increased p21 Expression.
2017 Mar
Involvement of heparanase in the pathogenesis of acute kidney injury: nephroprotective effect of PG545.
2017 May 23
A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours.
2018 Apr
Prophylactic Antiheparanase Activity by PG545 Is Antiviral In Vitro and Protects against Ross River Virus Disease in Mice.
2018 Apr
Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors.
2018 Jun 14

Sample Use Guides

25, 50, 100 and 150 mg once weekly for 28 days
Route of Administration: Intravenous
Substance Class Chemical
Created
by admin
on Sat Dec 16 11:55:42 GMT 2023
Edited
by admin
on Sat Dec 16 11:55:42 GMT 2023
Record UNII
66QR34C83N
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PIXATIMOD
INN  
Official Name English
Pixatimod [WHO-DD]
Common Name English
pixatimod [INN]
Common Name English
PG-545 FREE ACID
Code English
Code System Code Type Description
PUBCHEM
57412325
Created by admin on Sat Dec 16 11:55:43 GMT 2023 , Edited by admin on Sat Dec 16 11:55:43 GMT 2023
PRIMARY
SMS_ID
300000034341
Created by admin on Sat Dec 16 11:55:43 GMT 2023 , Edited by admin on Sat Dec 16 11:55:43 GMT 2023
PRIMARY
CAS
1144617-49-1
Created by admin on Sat Dec 16 11:55:43 GMT 2023 , Edited by admin on Sat Dec 16 11:55:43 GMT 2023
PRIMARY
INN
10685
Created by admin on Sat Dec 16 11:55:43 GMT 2023 , Edited by admin on Sat Dec 16 11:55:43 GMT 2023
PRIMARY
NCI_THESAURUS
C95202
Created by admin on Sat Dec 16 11:55:43 GMT 2023 , Edited by admin on Sat Dec 16 11:55:43 GMT 2023
PRIMARY
FDA UNII
66QR34C83N
Created by admin on Sat Dec 16 11:55:43 GMT 2023 , Edited by admin on Sat Dec 16 11:55:43 GMT 2023
PRIMARY
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SALT/SOLVATE -> PARENT
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ACTIVE MOIETY