Antitumor agent-37 has potent antiproliferation and antimetastatic activities. Antitumor agent-37 induces severe DNA damage and further leads to high expression of γ-H2AX and p53. Antitumor agent-37 promotes tumor cell apoptosis through the mitochondrial apoptosis pathway Bcl-2/Bax/caspase3. Antitumor agent-37 significantly improves the immune response by inhibiting the expression of PD-L1 to increase CD3+ and CD8+ T infiltrating cells in tumor tissues.

Physicochemical Properties

Molecular Formula	C16H20CL2N2O4PT
Molecular Weight	570.33
Appearance	Typically exists as solid at room temperature
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	apoptosis[1]
ln Vitro	Compound 7, or antitumor agent-37, exhibits comparatively decreased activities after 24 hours of treatment. The IC50 values also decrease at 48 hours, and the activities at 72 hours are comparable to those at 48 hours [1]. Significant tumor cell death is induced by agent-37 (compound 7) over the course of 24 hours in a dose-dependent manner[1]. Compound 7 (antitumor agent-37) activates the mitochondrial pathway Bcl-2/Bax/caspase3, causing tumor cells to undergo a significant apoptosis within 24 hours[1].
ln Vivo	Compound 7, also known as antitumor agent-37, exhibits low toxicity in vivo as evidenced by the fact that it has no discernible effect on mice's body weight when compared to the blank group four times on days 3, 6, 9, and 12 after tumor injection (4 mg Pt/kg). This is clearly superior to reference drug OLP and complex 9. Compound 7, or antitumor agent-37, likewise shows significant tumor growth inhibition to 4T1 tumors with a TGI of 54.6% when administered intraperitoneally (ip; 4 mg Pt/kg; four times on days 3, 6, 9, and 12 post-tumor inoculation)[1]. Compound 7, also known as antitumor agent-37 (ip; 2 mg Pt/kg; four times on days 2, 4, 6, 8, 10, 12, and 14 following tumor inoculation) exhibits antimetastasis effects in vivo that are noticeably more potent than those of CDDP and OLP[1].
Cell Assay	Apoptosis Analysis[1] Cell Types: murine tumor cell line 4T1 and human tumor cell line A549 Tested Concentrations: 5 and 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated effective apoptosis induction of both A549 and 4T1 cells after 24 h treatment. Western Blot Analysis[1] Cell Types: A549 cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Dramatically downregulated the level of anti-apoptotic Bcl-2 and increased the secretion of pro-apoptotic Bax. Subsequently, the apoptosis executor caspase3 and c-caspase3 were remarkably upregulated by antitumor agent-37.
Animal Protocol	Animal/Disease Models: Male balb/c (Bagg ALBino) mouse bearing CT-26 homograft tumors (18-20 g ); female balb/c (Bagg ALBino) mouse bearing murine 4T1 cells (18–20 g)[1] Doses: 4 mg Pt/kg Route of Administration: ip; four times on days 3, 6, 9, and 12 post-tumor inoculation Experimental Results: Exerted no visible impacts on body weight of mice in comparison with the blank group, which was obviously superior to reference drug OLP and complex 9, indicating its low toxicity in vivo. Antitumor agent-37 also demonstrated prominent tumor growth inhibition to 4T1 tumors with a TGI of 54.6%. Animal/Disease Models: balb/c (Bagg ALBino) mouse bearing murine 4T1 cells[1] Doses: 2 mg Pt/kg Route of Administration: ip; four times on days 2, 4, 6, 8, 10, 12, and 14 post-tumor inoculation Experimental Results: diminished metastatic nodules examined by H&E staining in the lung and obviously smaller than that from the blank group as well as CDDP and OLP groups.
References	[1]. Li Z, et al. Ketoprofen and Loxoprofen Platinum(IV) Complexes Displaying Antimetastatic Activities by Inducing DNA Damage, Inflammation Suppression, and Enhanced Immune Response. J Med Chem. 2021;64(24):17920-17935.

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	1.7534 mL	8.7669 mL	17.5337 mL
	5 mM	0.3507 mL	1.7534 mL	3.5067 mL
	10 mM	0.1753 mL	0.8767 mL	1.7534 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.