| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
| Targets |
The molecular targets of NSC 135130 are chemical functional groups, not biological targets. The linker is a BOC-protected intermediate that connects an antibody to a cytotoxic payload in an ADC. The final ADC targets a specific antigen on cancer cells (e.g., HER2, CD33, Trop-2). Upon antigen binding, the ADC is internalized, and the linker is designed to release the payload. The ultimate target of the payload (e.g., tubulin-targeting inhibitor) is the microtubule cytoskeleton, leading to cell cycle arrest and apoptosis. The BOC group masks an amine during synthesis of the linker-payload conjugate and is later removed under acidic conditions before conjugation to the antibody.
|
|---|---|
| ln Vitro |
NSC 135130 itself is a synthetic intermediate and is not biologically active. Its "in vitro activity" is defined by its utility in synthesizing drug-linker conjugates. The key step is removal of the BOC protecting group under acidic conditions (e.g., treatment with TFA in DCM) to reveal a free amine. This amine can then form an amide bond with a cytotoxic payload. BOC deprotection efficiency is typically >95% and can be monitored by TLC or HPLC. The resulting linker-payload is then conjugated to an antibody via standard methods (e.g., maleimide-thiol coupling). The final ADC is tested in cell-based assays for its ability to inhibit growth of antigen-positive cancer cells, with IC₅0 typically in low nanomolar range. The in vivo activity of an ADC made with this linker is evaluated in mouse xenograft models.
|
| Enzyme Assay |
A typical non-cellular assay for NSC 135130 is an analytical chemistry method to confirm structure and purity, such as HPLC and LC-MS. The efficiency of BOC deprotection can be monitored by TLC or HPLC. For example, NSC 135130 is dissolved in DCM and treated with an equal volume of TFA. The reaction is stirred at room temperature for 1-2 h. Solvent is removed under reduced pressure. The crude product is analyzed by LC-MS to confirm complete removal of the BOC group (mass decrease of ~100 Da). The yield of deprotection is calculated.
|
| Cell Assay |
In vitro cell-based activity of a completed ADC containing this linker is assessed using standard cytotoxicity assays. For example, if the ADC targets HER2, HER2-positive SK-BR-3 breast cancer cells are used. Cells are seeded in 96-well plates at 3 × 103 cells/well. Serial dilutions of the ADC (0.001-100 nM) are added. After 96 h, cell viability is measured using CellTiter-Glo. IC₅0 is calculated. The ADC's activity should be blocked by competition with excess unconjugated antibody. An isotype control ADC is used as negative control.
|
| Animal Protocol |
An in vivo animal study for an ADC made with this linker is performed in a xenograft model. Female BALB/c nude mice bearing established HER2-positive tumor xenografts (e.g., BT-474) are randomized (n=8-10) when tumors reach ~150 mm3. The ADC is formulated in 10 mM histidine buffer (pH 5.5) with 5% trehalose and 0.01% Tween-80, and administered intravenously at 3, 10, and 30 mg/kg once weekly for 3 weeks. Control receives vehicle. Tumor volumes are measured twice weekly. Body weight is monitored. Tumor growth inhibition (TGI) is calculated. At study end, tumors are excised for Ki-67 and TUNEL staining. All procedures require IACUC approval.
|
| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of NSC 135130 itself are not relevant, as it is a synthetic intermediate and not administered. The PK of an ADC made using this linker is dominated by the antibody component: long half-life (days), low clearance, low volume of distribution. The linker is designed to be stable in circulation and to release the payload effectively inside target cells.
|
| Toxicity/Toxicokinetics |
No toxicity data is available for NSC 135130. The toxicity of an ADC made using this linker is assessed in preclinical animal studies (rats and cynomolgus monkeys) and is related to the payload and the target antigen. Standard safety precautions should be used when handling this compound.
|
| References |
[1]. Malkov AV, Vranková K, Cerný M, Kocovský P. On the selective N-methylation of BOC-protected amino acids. J Org Chem. 2009 Nov 6;74(21):8425-7.
|
| Additional Infomation |
NSC 135130 is not an approved drug. It is a research-grade BOC-protected ADC linker used in the synthesis of drug-linker conjugates for targeted cancer therapy. Its mechanism is to provide a stable and cleavable linkage between an antibody and a tubulin-targeting inhibitor. It is a versatile intermediate for constructing ADCs. No clinical trials have been registered for NSC 135130. For research use only; not for diagnostic or therapeutic applications.
|
| Molecular Formula |
C12H23NO4
|
|---|---|
| Molecular Weight |
245.32
|
| Exact Mass |
245.163
|
| CAS # |
24164-06-5
|
| PubChem CID |
15655826
|
| Appearance |
Light yellow to yellow liquid
|
| Density |
1.015g/cm3
|
| Boiling Point |
293.5ºC at 760mmHg
|
| Flash Point |
131.3ºC
|
| Vapour Pressure |
0.00172mmHg at 25°C
|
| Index of Refraction |
1.448
|
| LogP |
2.05
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
17
|
| Complexity |
281
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O(C(N(C([H])([H])[H])C([H])(C(=O)OC([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H]
|
| InChi Key |
JHELVJNRWQYMIA-VIFPVBQESA-N
|
| InChi Code |
InChI=1S/C12H23NO4/c1-8(2)9(10(14)16-7)13(6)11(15)17-12(3,4)5/h8-9H,1-7H3/t9-/m0/s1
|
| Chemical Name |
methyl (2S)-3-methyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoate
|
| 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)
|
| 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
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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0763 mL | 20.3815 mL | 40.7631 mL | |
| 5 mM | 0.8153 mL | 4.0763 mL | 8.1526 mL | |
| 10 mM | 0.4076 mL | 2.0382 mL | 4.0763 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.
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
