| ln Vitro |
ISB2001 exhibits potent, affinity-driven tumor cell killing activity against a variety of multiple myeloma (MM) cell lines with EC50 values below the picomolar level [2]. ISB2001 remains effective against MM cells that have lost single antigens and overcomes antigen escape mechanisms that limit single antigen-targeted therapy [2]. ISB2001 is minimally affected by soluble factors (sBCMA, APRIL, sCD38) present in the serum of multiple myeloma (MM) patients, with its EC50 value increasing only 30-fold; in contrast, the EC50 value of BCMA targeting TCE increases significantly [2]. ISB2001 (0.01–1 nM) exhibits excellent cytotoxicity against primary multiple myeloma (MM) cells derived from bone marrow aspirate and peripheral blood, significantly killing CD138-positive tumor cells and activating CD8+ T cells [2].
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| ln Vivo |
ISB2001 (0.02–0.5 mg/kg, intravenously, once a week for 3 weeks) induced significant dose-dependent tumor growth inhibition and complete regression in the KMS-12-BM multiple myeloma xenograft model, accompanied by activation of tumor-infiltrating CD8+ T cells and increased levels of local pro-inflammatory cytokines [2]. ISB2001 (0.02–0.5 mg/kg, intravenously, once a week for 3 weeks) induced significant dose-dependent tumor growth inhibition and complete regression in the NCI-H929 multiple myeloma xenograft model [2]. ISB2001 (0.1–1 mg/kg, subcutaneously, once a week for 3 weeks) induced complete tumor regression in all humanized HIS-NXG mice treated with 1 mg/kg and caused partial persistent rejection in mice treated with 0.1 mg/kg [2]. ISB2001 (1.5 mg/kg; subcutaneous injection; single dose) did not induce depletion of CD38-expressing bone marrow hematopoietic progenitor cells or lymphocytes in humanized HIS-NXG mice, demonstrating good targeted antitumor safety profile [2].
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| Animal Protocol |
Animal/Disease Models:NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) (female, 6-7 weeks old) [2]
Doses: 0.02 mg/kg; 0.1 mg/kg; 0.5 mg/kg Route of Administration: Intravenous injection; once a week for 3 weeks Experimental Results: All dose groups significantly inhibited tumor growth compared with the solvent control group. The 0.5 mg/kg and 0.1 mg/kg dose groups induced complete tumor regression in all treated mice. The 0.02 mg/kg dose group induced partial efficacy and inhibited tumor growth compared with the solvent control group. Two days after treatment, compared with the vector control group mice (CD69+ 2.8%, CD25+ 0.0%) and the CD3×DU×DU treatment group mice (CD69+ 13.0%, CD25+ 0.0%), the expression of CD69 (84.3% positive cells) and CD25 (45.6% positive cells) in tumor-infiltrating CD8+ T cells was significantly increased. The concentrations of IFNγ (mean 100-250 ng/g tumor) and TNF (mean 1000-2500 pg/g tumor) in the tumor supernatant were increased, but no significant systemic cytokine activation was observed. Animal/Disease Models:NCG (NOD-Prkdcem26Cd52Il2rgem26Cd22/NjuCrl) (female, 6-7 weeks old) [2] Doses: 0.02 mg/kg; 0.1 mg/kg; 0.5 mg/kg Route of Administration: Intravenous injection; once a week for 3 weeks Experimental Results: All tested doses significantly inhibited tumor growth compared with the solvent control group. Complete tumor regression was induced in all treated mice at doses of 0.5 mg/kg and 0.1 mg/kg. Tumor growth was partially inhibited at dose of 0.02 mg/kg. Animal/Disease Models:HIS-NXG (Human Immune System-NOD-Prkdcscid-IL2rgTm1/Rj, reconstituted with human umbilical cord blood CD34+ cells) (female, 24-30 weeks old) [2] Doses: 0.1 mg/kg; 1 mg/kg Route of Administration: Subcutaneous injection; once a week; for 3 weeks Experimental Results: Tumors completely regressed in all mice in the 1 mg/kg dose group. All mice in the 0.1 mg/kg dose group showed a therapeutic response, and 4 out of 9 mice achieved durable tumor rejection; the remaining mice with palpable tumors showed significantly reduced tumor recurrence kinetics compared to the vector control group. |
| References |
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| Appearance |
Colorless to light yellow liquid
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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