Atamparib (RBN-2397; RBN2397) is a first-in-class, potent, orally bioactive and NAD+ competitive inhibitor of PARP7 (IC50<3 nM) with antitumor and immunomodulatory effects. It has activity across species. In order to restore interferon (Type I) signaling, RBN-2397 binds to PARP7 specifically. RBN-2397 has the potential to be used in research on solid tumors that have progressed or spread.

Physicochemical Properties

Molecular Formula	C₂₀H₂₃F₆N₇O₃
Molecular Weight	523.43
Exact Mass	523.18
Elemental Analysis	C, 45.89; H, 4.43; F, 21.78; N, 18.73; O, 9.17
CAS #	2381037-82-5
PubChem CID	146047148
Appearance	White to off-white solid powder
Density	1.53±0.1 g/cm3(Predicted)
LogP	1.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	14
Rotatable Bond Count	8
Heavy Atom Count	36
Complexity	848
Defined Atom Stereocenter Count	1
SMILES	FC(C1C([H])=NC(=NC=1[H])N1C([H])([H])C([H])([H])N(C(C([H])([H])C([H])([H])OC([H])([H])[C@]([H])(C([H])([H])[H])N([H])C2C([H])=NN([H])C(C=2C(F)(F)F)=O)=O)C([H])([H])C1([H])[H])(F)F
InChi Key	UQZCQKXJAXKZQH-LBPRGKRZSA-N
InChi Code	InChI=1S/C20H23F6N7O3/c1-12(30-14-10-29-31-17(35)16(14)20(24,25)26)11-36-7-2-15(34)32-3-5-33(6-4-32)18-27-8-13(9-28-18)19(21,22)23/h8-10,12H,2-7,11H2,1H3,(H2,30,31,35)/t12-/m0/s1
Chemical Name	4-[[(2S)-1-[3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy]propan-2-yl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one
Synonyms	RBN2397; RBN 2397; Atamparib; RBN-2397
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

Targets	PARP-7 ( IC50 = 3 nM ); PARP-7 ( Kd = 1 nM )
ln Vitro	RBN-2397 (0.0001-100 μM; 24 hours) inhibits cell proliferation with an IC50 value of 20 nM in NCI-H1373 lung cancer cells[2]. RBN-2397 (0.4 nM-1 μM; 24 hours) restores the type I IFN response in NCI-H1373 human lung cancer cells through a dose-dependent increase in STAT1 phosphorylation[2]. RBN-2397 (0.0001-1 μM; 24 hours) inhibits cell MARylation, with an EC50 value of 1 nM in a cell biochemial assay[2].
ln Vivo	RBN-2397 (oral administration; 3-100 mg/kg; once daily; 24-32 days) creates tumor-specific adaptive immune memory in CT26 syngeneic model in BALB/c mice bearing CT26 tumors, along with long-lasting full responses[2]. RBN-2397 (oral administration; 3-100 mg/kg; once daily; 32 days) inhibits tumor growth in a dose-dependent manner and causes complete regressions at 100 mg/kg at dose levels of ≥30 mg/kg[2]. RBN-2397 has a half-life (t1/2) of 325 minutes in vivo[2].
Cell Assay	Cell Line: NCI-H1373 lung cancer cells Concentration: 0.0001 μM; 0.001 μM; 0.001 μM; 0.1 μM; 1 μM; 10 μM; 100 μM Incubation Time: 24 hours Result: Blocked cell proliferation.
Animal Protocol	CB17 SCID mice with NCI-H1373 xenografts 3 mg/kg, 10mg/kg, 30 mg/kg, 100 mg/kg Oral administration; once daily; 24-32 days
References	[1]. RBN-2397-Inhibiting PARP7, a Key monoPARP Cancer Dependency. [2]. RBN-2397: A First-in-Class PARP7 Inhibitor Targeting a Newly Discovered Cancer Vulnerability in Stress-Signaling Pathways.
Additional Infomation	Atamparib is an orally available small molecule inhibitor of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) 7, with potential immunomodulating and antineoplastic activities. Upon oral administration,atamparib selectively binds to PARP7 and restores interferon (type 1) signaling. This may lead to the induction of both innate and adaptive immune responses, and the inhibition of tumor growth and proliferation. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA.

Solubility Data

Solubility (In Vitro)

DMSO: 100~200 mg/mL (191.0~382.1 mM) Ethanol: ~13 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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 2: ≥ 2.08 mg/mL (3.97 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 20.8 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 3: ≥ 2.08 mg/mL (3.97 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 20.8 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 4: ≥ 2.08 mg/mL (3.97 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 20.8 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 5: ≥ 0.5 mg/mL (0.96 mM) (saturation unknown) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 6: 5%DMSO+ 40%PEG300+ 5%Tween 80+ 50%ddH2O: 5.0mg/ml (9.55mM)  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9105 mL	9.5524 mL	19.1048 mL
	5 mM	0.3821 mL	1.9105 mL	3.8210 mL
	10 mM	0.1910 mL	0.9552 mL	1.9105 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.