Pelcitoclax (APG-1252) is a potent Bcl-2/Bcl-xl inhibitor (antagonist) with anti-tumor and pro-apoptotic effects.

Physicochemical Properties

Molecular Formula	C57H66CLF4N6O11PS4
Molecular Weight	1281.8479
Exact Mass	1280.303
CAS #	1619923-36-2
Related CAS #	BM-1244;1619923-32-8
PubChem CID	76900653
Appearance	White to off-white solid powder
LogP	7.5
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	21
Rotatable Bond Count	24
Heavy Atom Count	84
Complexity	2490
Defined Atom Stereocenter Count	1
SMILES	ClC1C([H])=C([H])C(=C([H])C=1[H])C1=C(C2C([H])=C(C([H])=C(C=2[H])N2C([H])([H])C([H])([H])N(C3C([H])=C([H])C(=C([H])C=3[H])N([H])S(C3C([H])=C([H])C(=C(C=3[H])S(C(F)(F)F)(=O)=O)N([H])[C@@]([H])(C([H])([H])SC3C([H])=C([H])C([H])=C([H])C=3[H])C([H])([H])C([H])([H])N3C([H])([H])C([H])([H])C([H])(C(=O)OC([H])([H])C([H])([H])C([H])([H])P(=O)(O[H])O[H])C([H])([H])C3([H])[H])(=O)=O)C([H])([H])C2([H])[H])F)C(=C(C([H])([H])[H])N1C([H])(C([H])([H])[H])C([H])([H])[H])S(C([H])([H])[H])(=O)=O
InChi Key	QIOCQCYXBYUYLH-YACUFSJGSA-N
InChi Code	InChI=1S/C57H66ClF4N6O11PS4/c1-38(2)68-39(3)55(82(4,73)74)53(54(68)40-11-13-43(58)14-12-40)42-33-44(59)35-48(34-42)67-29-27-66(28-30-67)47-17-15-45(16-18-47)64-84(77,78)50-19-20-51(52(36-50)83(75,76)57(60,61)62)63-46(37-81-49-9-6-5-7-10-49)23-26-65-24-21-41(22-25-65)56(69)79-31-8-32-80(70,71)72/h5-7,9-20,33-36,38,41,46,63-64H,8,21-32,37H2,1-4H3,(H2,70,71,72)/t46-/m1/s1
Chemical Name	3-[1-[(3R)-3-[4-[[4-[4-[3-[2-(4-chlorophenyl)-5-methyl-4-methylsulfonyl-1-propan-2-ylpyrrol-3-yl]-5-fluorophenyl]piperazin-1-yl]phenyl]sulfamoyl]-2-(trifluoromethylsulfonyl)anilino]-4-phenylsulfanylbutyl]piperidine-4-carbonyl]oxypropylphosphonic acid
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	In acute myeloid leukemia, APG-1252 transforms into the reactive metabolite APG-1252-M1, which has strong anticancer effects[1].
ln Vivo	Treatment with Pelcitoclax (APG-1252; 25-100 mg/kg; IV; once daily; for 10 days) slows the growth of xenograft tumors more clearly than other groups[1].
Animal Protocol	Animal/Disease Models: BALB/c athymic nude mice (male, 4-6weeks) injected with N87 cells[1] Doses: 25 mg/kg, 50 mg/kg, and 100 mg/kg Route of Administration: intravenous (iv)injection; one time/day; for 10 days Experimental Results: Inhibited xenograft tumor growth more obviously than the other groups.
References	[1]. Bcl-2/Bcl-xl inhibitor APG-1252-M1 is a promising therapeutic strategy for gastric carcinoma. Cancer Med. 2020 Jun;9(12):4197-4206.
Additional Infomation	Pelcitoclax is under investigation in clinical trial NCT04210037 (Study of Combination APG-1252 Plus Paclitaxel in Patients With Relapsed/refractory Small Cell Lung Cancer). Pelcitoclax is a Bcl-2 homology (BH)-3 mimetic and selective inhibitor of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Bcl-XL, with potential pro-apoptotic and antineoplastic activities. Upon administration, pelcitoclax specifically binds to and inhibits the activity of the pro-survival proteins Bcl-2 and Bcl-XL. This restores apoptotic processes and inhibits cell proliferation in Bcl-2/Bcl-XL-dependent tumor cells. Bcl-2 and Bcl-XL, proteins belonging to the Bcl-2 family that are overexpressed in many cancers, play an important role in the negative regulation of apoptosis; tumor expression is associated with increased drug resistance and cancer cell survival.

Solubility Data

Solubility (In Vitro)

DMSO : 200 mg/mL (156.02 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 5 mg/mL (3.90 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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 2: ≥ 5 mg/mL (3.90 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 50.0 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	0.7801 mL	3.9006 mL	7.8012 mL
	5 mM	0.1560 mL	0.7801 mL	1.5602 mL
	10 mM	0.0780 mL	0.3901 mL	0.7801 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.