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| Other Sizes |
| Targets |
Non-cleavable Linker
D-Proline, 4-hydroxy-, methyl ester hydrochloride does not have a classical pharmacological target. It serves as a chemical linker in the synthesis of bioconjugates. As a non-cleavable ADC linker, it is used to covalently attach cytotoxic drugs to antibodies for targeted cancer therapy. As a PROTAC linker, it connects a target protein ligand to an E3 ligase ligand. |
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| ln Vitro |
ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1]. Two distinct ligands, one for the E3 ubiquitin ligase and the other for the target protein, are present in PROTAC and are joined by a linker. PROTAC selectively degrades target proteins by means of the intracellular ubiquitin-proteasome system [2].
In vitro, D-Proline, 4-hydroxy-, methyl ester hydrochloride is characterized by its utility as a linker in bioconjugate chemistry. It is not evaluated for traditional pharmacological activity but rather for its chemical properties and compatibility with conjugation reactions. Its stability and reactivity in the synthesis of ADCs and PROTACs are key attributes. |
| ln Vivo |
In vivo, D-Proline, 4-hydroxy-, methyl ester hydrochloride is not used as a therapeutic agent itself. Its in vivo activity is realized through the ADCs or PROTACs that incorporate it as a linker. These conjugates can deliver cytotoxic payloads to tumor cells (ADCs) or induce targeted protein degradation (PROTACs) in vivo.
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| Enzyme Assay |
In vitro assays for D-Proline, 4-hydroxy-, methyl ester hydrochloride typically involve assessing its utility as a linker in conjugation reactions. The compound is used in the synthesis of ADC or PROTAC molecules. Its purity, stability, and reactivity are characterized by HPLC, NMR, and mass spectrometry. Conjugation efficiency to antibodies or target protein ligands is evaluated.
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| Cell Assay |
For in vitro cell-based assays, D-Proline, 4-hydroxy-, methyl ester hydrochloride is not typically used directly. Instead, the ADCs or PROTACs synthesized using this linker are evaluated for their biological activity. ADC activity is assessed by measuring target cell cytotoxicity. PROTAC activity is assessed by measuring target protein degradation via Western blot. Cell viability is assessed by MTT or standard assays.
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| Animal Protocol |
In vivo animal studies with D-Proline, 4-hydroxy-, methyl ester hydrochloride are not typically performed on the linker itself. The ADCs or PROTACs synthesized using this linker are evaluated in animal models. ADC efficacy is assessed in xenograft models by measuring tumor growth inhibition. PROTAC efficacy is assessed by measuring target protein degradation in tissues and tumor growth inhibition.
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| ADME/Pharmacokinetics |
D-Proline, 4-hydroxy-, methyl ester hydrochloride (CAS: 114676-59-4) has a molecular weight of 181.62 g/mol and a molecular formula of C6H12ClNO3. IUPAC name: methyl (2R,4R)-4-hydroxypyrrolidine-2-carboxylate hydrochloride. Appearance: solid. Storage: -20°C. The compound is a non-cleavable ADC linker and an alkyl chain-based PROTAC linker.
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| Toxicity/Toxicokinetics |
D-Proline, 4-hydroxy-, methyl ester hydrochloride is a research compound and is not approved for human therapeutic use. As a chemical linker, it is used in very small quantities in the synthesis of ADCs and PROTACs. Standard laboratory safety precautions should be followed when handling the compound. Comprehensive toxicology studies are not typically performed on the linker itself.
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| References |
[1]. Beck A, et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16(5):315-337.
[2]. Nalawansha DA, et al. PROTACs: An Emerging Therapeutic Modality in Precision Medicine. Cell Chem Biol. 2020;27(8):998-985. |
| Additional Infomation |
D-Proline, 4-hydroxy-, methyl ester hydrochloride ((4R)-4-hydroxy-D-proline methyl ester hydrochloride) is a chiral amino acid derivative with a molecular weight of 181.62 g/mol and a molecular formula of C6H12ClNO3. It is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates and an alkyl chain-based PROTAC linker. It is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C6H12CLNO3
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|---|---|
| Molecular Weight |
181.62
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| Exact Mass |
181.05
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| CAS # |
114676-59-4
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| PubChem CID |
12764090
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| Appearance |
White to off-white solid powder
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| Melting Point |
121-123 ºC
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| LogP |
0.013
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
11
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| Complexity |
137
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| Defined Atom Stereocenter Count |
2
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| SMILES |
COC(=O)[C@H]1C[C@H](CN1)O.Cl
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| InChi Key |
KLGSHNXEUZOKHH-TYSVMGFPSA-N
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| InChi Code |
InChI=1S/C6H11NO3.ClH/c1-10-6(9)5-2-4(8)3-7-5;/h4-5,7-8H,2-3H2,1H3;1H/t4-,5-;/m1./s1
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| Chemical Name |
methyl (2R,4R)-4-hydroxypyrrolidine-2-carboxylate;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.5060 mL | 27.5300 mL | 55.0600 mL | |
| 5 mM | 1.1012 mL | 5.5060 mL | 11.0120 mL | |
| 10 mM | 0.5506 mL | 2.7530 mL | 5.5060 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.
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