GL0388 is a Bax activator that causes Bax to insert into the mitochondrial membrane. GL0388 has antiproliferation activity against a variety of cancer cells with IC50 of 0.299-1.57 μM. GL0388 activates Bax and induces Bax-mediated apoptosis. GL0388 inhibits breast cancer xenograft tumor growth in vivo.

Physicochemical Properties

Molecular Formula	C21H17FN2O
Molecular Weight	332.370888471603
Exact Mass	332.132
CAS #	2886772-68-3
PubChem CID	162640853
Appearance	Light yellow to yellow solid powder
LogP	3.5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	25
Complexity	483
Defined Atom Stereocenter Count	0
SMILES	C1=CC=C\2C(=C1)C3=C(/C2=C/C4=C(N=CC=C4)OCCN)C=C(C=C3)F
InChi Key	WCVGRSPKTHQNCR-XDHOZWIPSA-N
InChi Code	InChI=1S/C21H17FN2O/c22-15-7-8-18-16-5-1-2-6-17(16)19(20(18)13-15)12-14-4-3-10-24-21(14)25-11-9-23/h1-8,10,12-13H,9,11,23H2/b19-12+
Chemical Name	2-[3-[(E)-(2-fluorofluoren-9-ylidene)methyl]pyridin-2-yl]oxyethanamine
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	Bax
ln Vitro	For MDA-MB-231 and MCF-7 breast cancer cell lines, GL0388 (0.1–10 μM; 72 h) suppresses cell growth with IC50s of 0.96 μM and 0.52 μM, respectively[1]. With GI550s of 0.299-1.57 μM, GL0388 (0.01-100 μM) suppresses the growth of 60 human tumor cell lines[1]. In MDA-MB-231 cells, GL0388 (1-10 μM; 48 h) dramatically increases the levels of cleaved PARP-1 and cleaved caspase 3 [1]. Breast cancer cell invasion and colony formation are inhibited by GL0388 (0.1–1 μM; 24 h)[1]. In a dose-dependent manner, GL0388 (1-10 μM; 24 h) facilitates Bax insertion into the mitochondrial membranes of MDA-MB-231 cells. In the cytosolic fraction of MDA-MB-231 cells, GL0388 raises cytochrome c[1].
ln Vivo	The growth of MDA-MB-231 tumors in mice is dose-dependently suppressed by GL0388 (10–20 mg/kg for ip; 15 mg/kg for it); administered once daily for 10 days[1].
Cell Assay	Cell Proliferation Assay[1] Cell Types: MCF-7, MDA-MB-231 cells Tested Concentrations: 0.1, 0.33, 1, 3.3, 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited the growth of MCF-7, MDA-MB-231 cells, with IC50s of 0.52 μM and 0.96 μM, respectively. Western Blot Analysis[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 1, 5, 10 μM Incubation Duration: 48 hrs (hours) Experimental Results: Dramatically led to the upregulation of cleaved PARP -1 and cleaved caspase 3.
Animal Protocol	Animal/Disease Models: Female nude mice were injected MDA-MB-231 cells[1] Doses: 10-20 mg/kg for ip; 15 mg/kg for it Route of Administration: Ip and it one time/day for 10 days Experimental Results: Dramatically inhibited tumor growth at a dose of 15 mg/kg every other day. IT administration for 10 days, with an inhibition rate of 55%, comparable to the IP efficacy at the dose of daily 20 mg/ kg.
References	[1]. Further lead optimization on Bax activators: Design, synthesis and pharmacological evaluation of 2-fluoro-fluorene derivatives for the treatment of breast cancer. Eur J Med Chem. 2021 Jul 5;219:113427.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	3.0087 mL	15.0435 mL	30.0870 mL
	5 mM	0.6017 mL	3.0087 mL	6.0174 mL
	10 mM	0.3009 mL	1.5043 mL	3.0087 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.