GUN55447 | CAS#136155-44-7

MedKoo Cat#: 556008 | Name: GUN55447

Description:

WARNING: This product is for research use only, not for human or veterinary use.

GUN55447 is a N-Acetyl calicheamicin (MedKoo Cat#: 408158) derivative, in which the -SSSMe side chain was replaced with a -SSC(Me)2CH2CH2CO2H. The carboxy group in GUN55447 is reactive to amino group after activation. GUN55447 is useful for making calicheamicin antibody conjugate (ADC). GUN55447 was first reported in Anal Chem. 1991 Nov 1;63(21):2470-81. doi: 10.1021/ac00021a016. This product has no formal name at the moment. For the convenience of communication, a temporary code name was therefore proposed according to MedKoo Chemical Nomenclature (see web page: https://www.medkoo.com/page/naming).

Chemical Structure

GUN55447

CAS#136155-44-7

Theoretical Analysis

MedKoo Cat#: 556008

Name: GUN55447

CAS#: 136155-44-7

Chemical Formula: C62H84IN3O24S3

Exact Mass: 1477.3652

Molecular Weight: 1478.43

Elemental Analysis: C, 50.37; H, 5.73; I, 8.58; N, 2.84; O, 25.97; S, 6.51

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

Bulk Inquiry

Related CAS #

No Data

Synonym

GUN55447; GUN-55447; GUN 55447; N-Acetyl calicheamicin derivative; N-acetyl gamma calicheamicin derivative.

IUPAC/Chemical Name

4-(((E)-2-((1R,8S,Z)-8-(((2R,3R,4S,5S,6R)-5-((((2S,4S,5S,6R)-5-((4-(((2S,3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-3-iodo-5,6-dimethoxy-2-methylbenzoyl)thio)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)amino)-3-(((2S,4S,5S)-5-(N-ethylacetamido)-4-methoxytetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-1-hydroxy-10-((methoxycarbonyl)amino)-11-oxobicyclo[7.3.1]trideca-4,9-dien-2,6-diyn-13-ylidene)ethyl)disulfanyl)-4-methylpentanoic acid

InChi Key

GVOMFGFJEUWBHH-UFDDPTQOSA-N

InChi Code

InChI=1S/C62H84IN3O24S3/c1-14-66(33(6)67)35-28-83-41(26-39(35)78-9)88-54-49(73)46(30(3)85-59(54)87-38-19-17-15-16-18-22-62(77)27-37(69)47(64-60(76)82-13)44(38)34(62)21-24-91-93-61(7,8)23-20-40(70)71)65-90-42-25-36(68)56(32(5)84-42)92-57(75)43-29(2)45(63)52(55(81-12)51(43)79-10)89-58-50(74)53(80-11)48(72)31(4)86-58/h15-16,21,30-32,35-36,38-39,41-42,46,48-50,53-54,56,58-59,65,68,72-74,77H,14,20,23-28H2,1-13H3,(H,64,76)(H,70,71)/b16-15-,34-21-/t30-,31+,32-,35+,36+,38+,39?,41+,42+,46-,48+,49+,50-,53-,54-,56-,58+,59+,62+/m1/s1

SMILES Code

CC(CCC(O)=O)(C)SSC/C=C([C@@]1(O)C2)/C([C@]([H])(C#C/C=C\C#C1)O[C@@H]3O[C@H](C)[C@@H](NO[C@@H]4O[C@H](C)[C@@H](SC(C5=C(C)C(I)=C(O[C@H]6[C@H](O)[C@H](OC)[C@@H](O)[C@H](C)O6)C(OC)=C5OC)=O)[C@@H](O)C4)[C@H](O)[C@H]3O[C@H]7C[C@H](OC)[C@@H](N(CC)C(C)=O)CO7)=C(NC(OC)=O)C2=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Antibody-drug conjugates (ADCs) have emerged as valuable targeted anticancer therapeutics with at least 11 approved therapies and over 80 advancing through clinical trials. Enediyne DNA-damaging payloads represented by the flagship of this family of antitumor agents, N-acetyl calicheamicin [Formula: see text], have a proven success track record. (copied from https://pubmed.ncbi.nlm.nih.gov/34155147/). The calicheamicins are a class of enediyne antitumor antibiotics derived from the bacterium Micromonospora echinospora,[1] with calicheamicin γ1 being the most notable.[2] It was isolated originally in the mid-1980s from the chalky soil, or "caliche pits", located in Kerrville, Texas. The sample was collected by a scientist working for Lederle Labs.[3] It is extremely toxic to all cells and, in 2000, a CD33 antigen-targeted immunoconjugate N-acetyl dimethyl hydrazide calicheamicin was developed and marketed as targeted therapy against the non-solid tumor cancer acute myeloid leukemia (AML).[4] A second calicheamicin-linked monoclonal antibody, inotuzumab ozogamicin (marketed as Besponsa) an anti-CD22-directed antibody-drug conjugate, was approved by the U.S. Food and Drug Administration on August 17, 2017, for use in the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.[5] Calicheamicin γ1 and the related enediyne esperamicin are the two of the most potent antitumor agents known.[6] Calicheamicins target DNA and cause strand scission. Calicheamicins bind with DNA in the minor groove, wherein they then undergo a reaction analogous to the Bergman cyclization to generate a diradical species. This diradical, 1,4-didehydrobenzene, then abstracts hydrogen atoms from the deoxyribose (sugar) backbone of DNA, which ultimately leads to strand scission.[7] The specificity of binding of calicheamicin to the minor groove of DNA was demonstrated by Crothers et al. (1999) to be due to the aryltetrasaccharide group of the molecule.[8][9] (copied from https://en.wikipedia.org/wiki/Calicheamicin)

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 1,478.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

1: Nicolaou KC, Rigol S, Pitsinos EN, Das D, Lu Y, Rout S, Schammel AW, Holte D, Lin B, Gu C, Sarvaiya H, Trinidad J, Barbour N, Valdiosera AM, Sandoval J, Lee C, Aujay M, Fernando H, Dhar A, Karsunky H, Taylor N, Pysz M, Gavrilyuk J. Uncialamycin-based antibody-drug conjugates: Unique enediyne ADCs exhibiting bystander killing effect. Proc Natl Acad Sci U S A. 2021 Jun 22;118(25):e2107042118. doi: 10.1073/pnas.2107042118. PMID: 34155147. 2: Hibma J, Knight B. Population Pharmacokinetic Modeling of Gemtuzumab Ozogamicin in Adult Patients with Acute Myeloid Leukemia. Clin Pharmacokinet. 2019 Mar;58(3):335-347. doi: 10.1007/s40262-018-0699-5. PMID: 30062662. 3: Masters JC, Barry E, Knight B. Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia. Clin Pharmacokinet. 2019 Feb;58(2):271-282. doi: 10.1007/s40262-018-0694-x. PMID: 30022367. 4: Azuma Y, Nakaya A, Hotta M, Fujita S, Tsubokura Y, Yoshimura H, Satake A, Ishii K, Ito T, Nomura S. Disseminated intravascular coagulation observed following treatment with gemtuzumab ozogamicin for relapsed/refractory acute promyelocytic leukemia. Mol Clin Oncol. 2016 Jul;5(1):31-34. doi: 10.3892/mco.2016.864. Epub 2016 Apr 20. PMID: 27330760; PMCID: PMC4906953. 5: Duong HK, Sekeres MA. Targeted treatment of acute myeloid leukemia in older adults: role of gemtuzumab ozogamicin. Clin Interv Aging. 2009;4():197-205. doi: 10.2147/cia.s3968. Epub 2009 May 14. PMID: 19503782; PMCID: PMC2685241. 6: Stasi R, Evangelista ML, Buccisano F, Venditti A, Amadori S. Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. Cancer Treat Rev. 2008 Feb;34(1):49-60. doi: 10.1016/j.ctrv.2007.09.001. Epub 2007 Oct 17. PMID: 17942233. 7: Boghaert ER, Sridharan L, Armellino DC, Khandke KM, DiJoseph JF, Kunz A, Dougher MM, Jiang F, Kalyandrug LB, Hamann PR, Frost P, Damle NK. Antibody- targeted chemotherapy with the calicheamicin conjugate hu3S193-N-acetyl gamma calicheamicin dimethyl hydrazide targets Lewisy and eliminates Lewisy-positive human carcinoma cells and xenografts. Clin Cancer Res. 2004 Jul 1;10(13):4538-49. doi: 10.1158/1078-0432.CCR-04-0037. PMID: 15240546. 8: DiJoseph JF, Armellino DC, Boghaert ER, Khandke K, Dougher MM, Sridharan L, Kunz A, Hamann PR, Gorovits B, Udata C, Moran JK, Popplewell AG, Stephens S, Frost P, Damle NK. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood. 2004 Mar 1;103(5):1807-14. doi: 10.1182/blood-2003-07-2466. Epub 2003 Nov 13. PMID: 14615373. 9: Giles F, Estey E, O'Brien S. Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. Cancer. 2003 Nov 15;98(10):2095-104. doi: 10.1002/cncr.11791. PMID: 14601078. 10: Dowell JA, Korth-Bradley J, Liu H, King SP, Berger MS. Pharmacokinetics of gemtuzumab ozogamicin, an antibody-targeted chemotherapy agent for the treatment of patients with acute myeloid leukemia in first relapse. J Clin Pharmacol. 2001 Nov;41(11):1206-14. doi: 10.1177/00912700122012751. PMID: 11697753. 11: Hinman LM, Hamann PR, Wallace R, Menendez AT, Durr FE, Upeslacis J. Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics. Cancer Res. 1993 Jul 15;53(14):3336-42. PMID: 8324745.