| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Talirine is a PBD-based drug-linker that targets DNA. PBDs are sequence-selective DNA minor-groove binding crosslinking agents. In the context of an ADC, it is designed to be delivered to cancer cells expressing a specific target, such as CD33 in acute myeloid leukemia (AML).
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|---|---|
| ln Vitro |
ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1].
As a PBD dimer, Talirine is a highly potent cytotoxic agent. In vitro, it functions by binding to DNA in the minor groove and forming crosslinks, which prevents DNA replication and transcription, leading to cell death. Its potency is significantly greater than that of systemic chemotherapeutic drugs. |
| ln Vivo |
In vivo activity is demonstrated through its use in ADCs, such as vadastuximab talirine, which targets CD33-positive cells. The ADC delivers Talirine specifically to AML cells, allowing for targeted cell killing. The in vivo efficacy is dependent on the targeting antibody.
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| Enzyme Assay |
The DNA-binding activity of PBD dimers like Talirine is characterized in cell-free systems. These assays measure the compound's ability to bind to DNA and form crosslinks, which is the basis of its mechanism of action.
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| Cell Assay |
Talirine's activity is assessed in cell-based assays as part of an ADC. The potency of the ADC is measured by its ability to kill target antigen-expressing cancer cells. Its high potency is a key feature of its profile.
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| Animal Protocol |
In vivo efficacy of Talirine-based ADCs is evaluated in animal models, typically xenograft models of human cancers. The ADC's ability to inhibit tumor growth is measured, demonstrating the targeted delivery and potent anti-tumor activity of the PBD payload.
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| ADME/Pharmacokinetics |
As a drug-linker, the pharmacokinetics of Talirine are largely determined by the ADC's properties. The ADC is designed to be stable in circulation, releasing the potent PBD payload specifically within the target cell.
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| Toxicity/Toxicokinetics |
The toxicity of Talirine is related to its mechanism of action. As a highly potent DNA crosslinking agent, its primary toxicity would be expected to be myelosuppression and other effects associated with DNA damage. However, the targeted delivery via an ADC aims to minimize these off-target toxicities.
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| References |
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| Additional Infomation |
Talirine is a key component in the development of ADCs for targeted cancer therapy. Its use in vadastuximab talirine for the treatment of AML highlights its potential in oncology. As a foundational PBD-based drug-linker, it is a valuable tool for ADC development.
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| Molecular Formula |
C60H64N8O12
|
|---|---|
| Molecular Weight |
1089.20000
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| Exact Mass |
1088.46
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| CAS # |
1342820-51-2
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| PubChem CID |
89396500
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| Appearance |
White to yellow solid powder
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| LogP |
7.112
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
23
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| Heavy Atom Count |
80
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| Complexity |
2390
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C[C@@H](C(=O)NC1=CC=C(C=C1)C2=CN3[C@@H](C2)C=NC4=CC(=C(C=C4C3=O)OC)OCCCOC5=C(C=C6C(=C5)N=C[C@@H]7CC(=CN7C6=O)C8=CC=C(C=C8)OC)OC)NC(=O)[C@H](C(C)C)NC(=O)CCCCCN9C(=O)C=CC9=O
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| InChi Key |
TWQIMWSQDICMSE-DGCIIGOYSA-N
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| InChi Code |
InChI=1S/C60H64N8O12/c1-35(2)56(65-53(69)11-8-7-9-22-66-54(70)20-21-55(66)71)58(73)63-36(3)57(72)64-41-16-12-37(13-17-41)39-25-42-31-61-47-29-51(49(77-5)27-45(47)59(74)67(42)33-39)79-23-10-24-80-52-30-48-46(28-50(52)78-6)60(75)68-34-40(26-43(68)32-62-48)38-14-18-44(76-4)19-15-38/h12-21,27-36,42-43,56H,7-11,22-26H2,1-6H3,(H,63,73)(H,64,72)(H,65,69)/t36-,42-,43-,56-/m0/s1
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| Chemical Name |
N-[(2S)-1-[[(2S)-1-[4-[(6aS)-3-[3-[[(6aS)-2-methoxy-8-(4-methoxyphenyl)-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-2-methoxy-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]anilino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-6-(2,5-dioxopyrrol-1-yl)hexanamide
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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) |
DMSO : ~50 mg/mL (~45.91 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (0.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9181 mL | 4.5905 mL | 9.1811 mL | |
| 5 mM | 0.1836 mL | 0.9181 mL | 1.8362 mL | |
| 10 mM | 0.0918 mL | 0.4591 mL | 0.9181 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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