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MC-GGFG-DX8951, a DX8951 analog with antitumor activity, is a drug-linker conjugate used for synthesis of antibody drug conjugate (ADC) where DX8951 serves as a payload/warhead. It has a MC-GGFG linker, in which DX8951 was covalently connected via a peptidyl spacer (Gly-Gly-Phe-Gly), which is assumed to be stable in circulation, and were cleaved by lysosomal enzymes following ADC internalization into tumor tissue. MC-GGFG-DX8951 is very useful to prepare DX8951 antibody drug conjugate (ADC).
| Targets |
Topoisomerase; Camptothecins
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|---|---|
| ln Vitro |
Lysosomal enzymes—possibly cathepsins—selectively cleave GGFG in MC-GGFG-Exatecan [1].
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| ln Vivo |
It is known that GGFG releases medications into tumor tissue in MC-GGFG-Exatecan rather than into the peripheral circulation [1].
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| References | |
| Additional Infomation |
Trastuzumab conjugates consisting of exatecan derivatives were prepared and their biological activities and physicochemical properties were evaluated. The ADCs showed strong efficacy and a low aggregation rate. The exatecan derivatives were covalently connected via a peptidyl spacer (Gly-Gly-Phe-Gly), which is assumed to be stable in circulation, and were cleaved by lysosomal enzymes following ADC internalization into tumor tissue. These anti-HER2 ADCs exhibited a high potency, specifically against HER2-positive cancer cell lines in vitro. The ADCs, bearing exatecan derivatives which have more than two methylene chains, exhibited superior cytotoxicity. It was speculated that steric hindrance of the cleavable amide moiety could be involved in the drug release. The adequate alkyl lengths of exatecan derivatives (13, 14, 15) were from two to four in terms of aggregation rate. The ADC having a hydrophilic moiety showed good efficacy in a HER2-positive and Trastuzumab-resistant breast carcinoma cell model in mice. [1]
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| Molecular Formula |
C49H51FN8O11
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|---|---|
| Molecular Weight |
946.9747
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| Exact Mass |
946.366
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| CAS # |
1600418-29-8
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| PubChem CID |
118567450
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
0.3
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| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
18
|
| Heavy Atom Count |
69
|
| Complexity |
2180
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
FC1C([H])=C2C3=C(C=1C([H])([H])[H])C([H])([H])C([H])([H])[C@@]([H])(C3=C1C(C3=C([H])C4[C@](C(=O)OC([H])([H])C=4C(N3C1([H])[H])=O)(C([H])([H])C([H])([H])[H])O[H])=N2)N([H])C(C([H])([H])N([H])C([C@]([H])(C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])N([H])C(C([H])([H])N([H])C(C([H])([H])N([H])C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C(C([H])=C([H])C1=O)=O)=O)=O)=O)=O)=O
|
| InChi Key |
XEKFDUNPKACYAY-UAVZYSABSA-N
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| InChi Code |
InChI=1S/C49H51FN8O11/c1-3-49(68)31-19-36-45-29(24-58(36)47(66)30(31)25-69-48(49)67)44-33(14-13-28-26(2)32(50)20-34(56-45)43(28)44)54-40(62)23-53-46(65)35(18-27-10-6-4-7-11-27)55-39(61)22-52-38(60)21-51-37(59)12-8-5-9-17-57-41(63)15-16-42(57)64/h4,6-7,10-11,15-16,19-20,33,35,68H,3,5,8-9,12-14,17-18,21-25H2,1-2H3,(H,51,59)(H,52,60)(H,53,65)(H,54,62)(H,55,61)/t33-,35+,49+/m1/s1
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| Chemical Name |
6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-(2-((2-(((S)-1-((2-(((1R,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4'
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| Synonyms |
MC-GGFG-DX8951; MC-GGFG-DX-8951; MC-GGFG-DX8951; 1600418-29-8; MC-GGFG-Exatecan; 6-(2,5-dioxopyrrol-1-yl)-N-[2-[[2-[[(2S)-1-[[2-[[(10S,23S)-10-ethyl-18-fluoro-10-hydroxy-19-methyl-5,9-dioxo-8-oxa-4,15-diazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16,18,20(24)-heptaen-23-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]hexanamide; Trastuzumab Impurity 1; N5T2U2WX4G; MC-GGFG-DX8951?; SCHEMBL17325024; MC-GGFG-DX 8951; MC-GGFG-DX.
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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) |
DMSO : ~50 mg/mL (~52.80 mM)
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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 | 1.0560 mL | 5.2800 mL | 10.5600 mL | |
| 5 mM | 0.2112 mL | 1.0560 mL | 2.1120 mL | |
| 10 mM | 0.1056 mL | 0.5280 mL | 1.0560 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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