BM-1197 (UBX1967) is a potent and specific dual Bcl-2/Bcl-xL inhibitor (antagonist) with IC50s of 3.5 nM and 5.2 nM for Bcl-2 and Bcl-xL inhibition, respectively. BM-1197 displays antitumor effects both in vitro and in vivo.

Physicochemical Properties

Molecular Formula	C53H59CLF4N6O7S4
Molecular Weight	1131.77818131447
Exact Mass	1130.295
CAS #	1391107-89-3
PubChem CID	60204010
Appearance	White to light yellow solid powder
LogP	10.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	17
Rotatable Bond Count	18
Heavy Atom Count	75
Complexity	2140
Defined Atom Stereocenter Count	1
SMILES	C1(S(NC2=CC=C(N3CCN(C4=CC(F)=CC(C5C(S(C)(=O)=O)=C(C)N(C(C)C)C=5C5=CC=C(Cl)C=C5)=C4)CC3)C=C2)(=O)=O)=CC=C(N[C@@H](CSC2=CC=CC=C2)CCN2CCC(O)CC2)C(S(C(F)(F)F)(=O)=O)=C1
InChi Key	DMKVQMFONHHNMZ-HUESYALOSA-N
InChi Code	InChI=1S/C53H59ClF4N6O7S4/c1-35(2)64-36(3)52(73(4,66)67)50(51(64)37-10-12-39(54)13-11-37)38-30-40(55)32-44(31-38)63-28-26-62(27-29-63)43-16-14-41(15-17-43)60-75(70,71)47-18-19-48(49(33-47)74(68,69)53(56,57)58)59-42(34-72-46-8-6-5-7-9-46)20-23-61-24-21-45(65)22-25-61/h5-19,30-33,35,42,45,59-60,65H,20-29,34H2,1-4H3/t42-/m1/s1
Chemical Name	N-[4-[4-[3-[2-(4-chlorophenyl)-5-methyl-4-methylsulfonyl-1-propan-2-ylpyrrol-3-yl]-5-fluorophenyl]piperazin-1-yl]phenyl]-4-[[(2R)-4-(4-hydroxypiperidin-1-yl)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)benzenesulfonamide
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	Bcl-2 3.5 nM (IC50) Bcl-xL 5.2 nM (IC50)
ln Vitro	In MCL1−/− cells, BM-1197 (2-2000 nM; 3 d) exhibits strong growth-inhibitory activity, although it is only slightly cytotoxic to wild-type mouse embryonic fibroblast (MEF) cells[1]. Seven small cell lung cancer (SCLC) cell lines with IC50s <100 nM, three with IC50s of around 600 nM, and two with IC50s >2000 nM exhibit strong growth-inhibitory activities in response to BM-1197[1]. H146 cells are potently exposed to BM-1197 (100 nM; 16 h) to trigger apoptosis[1]. In H146 cells, the relationship between Bcl-xl and Puma or Bim is broken by BM-1197 (100 nM; 2 h)[1]. Bax translocation and cytochrome c release are both induced by 1197 (100 nM; 0.5-2 h) and 3-30 nM; 2 h), respectively, in H146 cells[1].
ln Vivo	In the H146 and H1963 tumor model, BM-1197 (10 mg/kg; intravenous daily, five days a week for two weeks) causes quick and total tumor regression in all eight mice[1]. Mice treated with BM-1197 (15 mg/kg; IV) exhibit thrombocytopenia, although even at very effective doses, the condition is reversible[1]. In OCI-Ly8 xenograft models, BM-1197 (10 mg/kg; iv qd) is well tolerated and has a potent anti-tumor effect[2].
Cell Assay	Cell Proliferation Assay[1] Cell Types: MEF/MCL1−/− cells Tested Concentrations: 2, 20, 200, 2000 nM Incubation Duration: 3 days Experimental Results: Inhibited MCL1−/− cells proliferation. Apoptosis Analysis[1] Cell Types: H146 cells Tested Concentrations: 100 nM Incubation Duration: 16 hrs (hours) Experimental Results: Induced apoptosis in a strictly Bax/Bak-dependent manner. Western Blot Analysis[1] Cell Types: H146 cells Tested Concentrations: 100 nM Incubation Duration: 2 hrs (hours) Experimental Results: Attenuated the associations between Bcl-xL and BimEL or Puma.
Animal Protocol	Animal/Disease Models: SCID (severe combined immunodeficient) mouse bearing H146 cells[1] Doses: 10 mg/kg Route of Administration: Iv daily 5 days per week for 2 weeks Experimental Results: Remained tumor free for at least 32 days after the end of the treatment.
References	[1]. BM-1197: a novel and specific Bcl-2/Bcl-xL inhibitor inducing complete and long-lasting tumor regression in vivo. PLoS One. 2014 Jun 5; 9(6): e99404. [2]. A novel Bcl-2 inhibitor, BM-1197, induces apoptosis in malignant lymphoma cells through the endogenous apoptotic pathway. BMC Cancer. 2019 Dec 31; 20(1):1.

Solubility Data

Solubility (In Vitro)

DMSO : 250 mg/mL (220.89 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.8836 mL	4.4178 mL	8.8356 mL
	5 mM	0.1767 mL	0.8836 mL	1.7671 mL
	10 mM	0.0884 mL	0.4418 mL	0.8836 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.