PDD00017273 is a novel, potent and selective poly (ADP ribose) glycohydrolase (PARG) inhibitor with an IC50 of 26 nM. PDD00017273 exhibits >350-fold selectivity for PARG over a panel of ion channels, enzymes and receptors, including PARP1 and ARH3.
Physicochemical Properties
| Molecular Formula | C23H26N6O4S2 |
| Molecular Weight | 514.6203 |
| CAS # | 1945950-21-9 |
| Related CAS # | 1945950-21-9; |
| PubChem CID | 121398766 |
| Appearance | White to light yellow solid powder |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 35 |
| Complexity | 954 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S(C1C=CC2=C(C(N(CC3=CN=C(C)S3)C(N2CC2=CC(C)=NN2C)=O)=O)C=1)(NC1(C)CC1)(=O)=O |
| InChi Key | IFWUBRBMMNTBRZ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C23H26N6O4S2/c1-14-9-16(27(4)25-14)12-28-20-6-5-18(35(32,33)26-23(3)7-8-23)10-19(20)21(30)29(22(28)31)13-17-11-24-15(2)34-17/h5-6,9-11,26H,7-8,12-13H2,1-4H3 |
| Chemical Name | 1-[(1,3-Dimethyl-1H-pyrazol-5-yl)methyl]-1,2,3,4-tetrahydro-N-(1-methylcyclopropyl)-3-[(2-methyl-5-thiazolyl)methyl]-2,4-dioxo-6-quinazolinesulfonamide |
| Synonyms | PDD-00017273 PDD 00017273 PDD00017273 PDD-17273 PDD 17273 PDD 17273 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | PDD 00017273 is a powerful PARG reagent with an IC50 of 26 nM and a KD of 1.45 nM. For five typical cytochrome P450 enzymes, PDD 00017273 (10 μM) does not inhibit. In addition to inhibiting NAD/H through PARG after DNA damage, PDD 00017273 (30 μM) increases the intensity of phosphorylated H2AX (γH2AX). When it comes to MDA-MB-436 cells labeled with 5396 + 1G>A in BRCA1, PDD 00017273 exhibits minimal activity, but it inhibits ZR-75-1 cells labeled with wild-type BRCA1 and BRCA2 [1]. The breakdown of PAR medium in MCF7 cells is inhibited by PDD 00017273 (0.3 μM). Additionally, BARD1, BRCA2, PALB2, FAM175A, and BRCA1 latency are decreased by PDD 00017273 (0.3 μM). Inducing DNA damage that must be repaired by homologous recombination (HR) and stopping replication forks are the effects of PDD 00017273 [2]. |
| References |
[1]. First-in-Class Chemical Probes against Poly(ADP-ribose) Glycohydrolase (PARG) Inhibit DNA Repair with Differential Pharmacology to AZD2281. ACS Chem Biol. 2016 Nov 18;11(11):3179-3190. Epub 2016 Oct 12. [2]. Specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase. DNA Repair (Amst). 2017 Apr;52:81-91. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~25 mg/mL (~48.58 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9432 mL | 9.7159 mL | 19.4318 mL | |
| 5 mM | 0.3886 mL | 1.9432 mL | 3.8864 mL | |
| 10 mM | 0.1943 mL | 0.9716 mL | 1.9432 mL |