abt-510 profile

NAc-Sar-Gly-Val-(d-allo-Ile)-Thr-Nva-Ile-Arg-ProNEt: has antiangiogenic and antineoplastic activity; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	6918562
CHEMBL ID	386115
MeSH ID	M0522043

Synonym
abt-510
nac-sar-gly-val-(d-allo-ile)-thr-nva-ile-arg-pronet
abt 510
abt-526
CHEMBL386115
(2s)-1-[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2s,3r)-2-[[(2r,3s)-2-[[(2s)-2-[[2-[[2-[acetyl(methyl)amino]acetyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]pentanoyl]amino]-3-methylpentanoyl]amino]-5-(diaminomethy
crr8e37xob ,
unii-crr8e37xob
l-prolinamide, n-acetyl-n-methylglycylglycyl-l-valyl-d-alloisoleucyl-l-threonyl-l-norvalyl-l-isoleucyl-l-arginyl-n-ethyl-
251579-55-2
abt 510 [who-dd]
DB05434
Q27095674
(2s)-1-[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2s,3s)-2-[[(2r,3s)-2-[[(2s)-2-[[2-[[2-[acetyl(methyl)amino]acetyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]pentanoyl]amino]-3-methylpentanoyl]amino]-5-(diaminomethy
HY-13545
CS-0007141
DTXSID80870283
(s)-n-ethyl-1-(((s)-2-((2s,3r)-3-hydroxy-2-((2r,3s)-3-methyl-2-((s)-3-methyl-2-(2-(2-(n-methylacetamido)acetamido)acetamido)butanamido)pentanamido)butanamido)pentanoyl)-l-isoleucyl-l-arginyl)pyrrolidine-2-carboxamide

Excerpt	Reference	Relevance
" The most common reported adverse events reflected the known toxicity profile induced by gemcitabine-cisplatin without ABT-510."	( A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors. Carr, RA; de Vos, FY; Eskens, FA; Gietema, JA; Groen, HJ; Hoekstra, R; Humerickhouse, RA; Knight, RA; Loos, WJ; Uges, DR; van der Gaast, A, 2006)	0.75

Excerpt	Reference	Relevance
" However, therapeutic utility could not be demonstrated because this peptide has a very short half-life in rodents."	( Thrombospondin-1 mimetic peptide inhibitors of angiogenesis and tumor growth: design, synthesis, and optimization of pharmacokinetics and biological activities. Badylak, SF; Bell, RL; Bradley, MF; Davidson, DJ; Ferrero, J; Haskell, CJ; Haviv, F; Henkin, J; Hodde, J; Kalvin, DM; Leal, J; Lesniewski, RR; Majest, SM; Marsh, KC; McKay, LM; Nguyen, B; Record, RD; Schneider, AJ; Surber, BW; Uchic, JT; Wang, YC, 2005)	0.33
" No clinically significant pharmacokinetic interactions between ABT-510, gemcitabine and platinum were observed."	( A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors. Carr, RA; de Vos, FY; Eskens, FA; Gietema, JA; Groen, HJ; Hoekstra, R; Humerickhouse, RA; Knight, RA; Loos, WJ; Uges, DR; van der Gaast, A, 2006)	0.78
" Pharmacokinetic interactions were not observed and adding ABT-510 does not appear to increase toxicity."	( A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors. Carr, RA; de Vos, FY; Eskens, FA; Gietema, JA; Groen, HJ; Hoekstra, R; Humerickhouse, RA; Knight, RA; Loos, WJ; Uges, DR; van der Gaast, A, 2006)	0.79

Excerpt	Reference	Relevance
" Our results indicate that ABT-510 combined with VPA may be an effective antiangiogenic treatment strategy for children with high-risk neuroblastoma."	( Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Chlenski, A; Cohn, SL; Henkin, J; Liu, S; Salwen, HR; Tian, Y; Yang, Q; Zeine, R, 2007)	0.94

Excerpt	Relevance	Reference
" ABT-510 pharmacokinetics were linear across the dosage ranges tested, and the potential therapeutic threshold (plasma concentrations > 100 ng/mL > 3 h/d) was achieved with all dose regimens."	( Phase I safety, pharmacokinetic, and pharmacodynamic study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 in patients with advanced cancer. Carr, RA; de Vos, FY; de Vries, EG; Eskens, FA; Gietema, JA; Groen, HJ; Hoekstra, R; Humerickhouse, RA; Knight, RA; van der Gaast, A; Verweij, J, 2005)	1.45
" The significant number of patients with prolonged stable disease and the convenient method of dosing merit further studies with this angiogenesis inhibitor."	( Phase I safety, pharmacokinetic, and pharmacodynamic study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 in patients with advanced cancer. Carr, RA; de Vos, FY; de Vries, EG; Eskens, FA; Gietema, JA; Groen, HJ; Hoekstra, R; Humerickhouse, RA; Knight, RA; van der Gaast, A; Verweij, J, 2005)	0.54
" The current study was designed to establish the safety of ABT-510 in the treatment of patients with advanced malignancies on a once-daily (QD) and twice-daily dosing schedule."	( A phase 1 trial of 2 dose schedules of ABT-510, an antiangiogenic, thrombospondin-1-mimetic peptide, in patients with advanced cancer. Carr, R; Gordon, MS; Humerickhouse, RA; Iannone, M; Knight, RA; Mendelson, D; Stopeck, AT, 2008)	0.86
"Patients were randomly assigned to 1 of 6 dosing regimens: 20 mg, 50 mg, or 100 mg QD or 10 mg, 25 mg, or 50 mg twice daily."	( A phase 1 trial of 2 dose schedules of ABT-510, an antiangiogenic, thrombospondin-1-mimetic peptide, in patients with advanced cancer. Carr, R; Gordon, MS; Humerickhouse, RA; Iannone, M; Knight, RA; Mendelson, D; Stopeck, AT, 2008)	0.62
" We determined that 8 weeks of 100 microg/mL 4-NQO in the drinking water was the optimal dosage and duration to cause a sufficient incidence of hyperkeratoses, dysplasias, and HNSCC over a period of 32 weeks with minimal morbidity and mortality."	( ABT-510 is an effective chemopreventive agent in the mouse 4-nitroquinoline 1-oxide model of oral carcinogenesis. Hasina, R; Jalil, A; Jones, CL; Kasza, K; Lingen, MW; Martin, LE, 2009)	1.8

Assay ID	Title	Year	Journal	Article
AID247823	Inhibitory concentration against TSP-1 binding towards HMVEC cell line migration	2005	Journal of medicinal chemistry, Apr-21, Volume: 48, Issue:8	Thrombospondin-1 mimetic peptide inhibitors of angiogenesis and tumor growth: design, synthesis, and optimization of pharmacokinetics and biological activities.
AID248612	In vitro inhibitory concentration against HMVEC endothelial tube formation was determined; 10 - 5.0 nM	2005	Journal of medicinal chemistry, Apr-21, Volume: 48, Issue:8	Thrombospondin-1 mimetic peptide inhibitors of angiogenesis and tumor growth: design, synthesis, and optimization of pharmacokinetics and biological activities.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	21 (77.78)	29.6817
2010's	5 (18.52)	24.3611
2020's	1 (3.70)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	10 (35.71%)	5.53%
Reviews	0 (0.00%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	18 (64.29%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
valproic acid Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. valproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.	7.03	1	0	branched-chain fatty acid; branched-chain saturated fatty acid	anticonvulsant; antimanic drug; EC 3.5.1.98 (histone deacetylase) inhibitor; GABA agent; neuroprotective agent; psychotropic drug; teratogenic agent
fluorouracil Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. 5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth.	8.41	1	1	nucleobase analogue; organofluorine compound	antimetabolite; antineoplastic agent; environmental contaminant; immunosuppressive agent; radiosensitizing agent; xenobiotic
temozolomide [no description available]	3.44	1	1	imidazotetrazine; monocarboxylic acid amide; triazene derivative	alkylating agent; antineoplastic agent; prodrug
4-nitroquinoline-1-oxide 4-nitroquinoline N-oxide : A quinoline N-oxide carrying a nitro substituent at position 4.	2.05	1	0	C-nitro compound; quinoline N-oxide	carcinogenic agent
deoxycytidine [no description available]	3.41	1	1	pyrimidine 2'-deoxyribonucleoside	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
paclitaxel Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).	7.05	1	0	taxane diterpenoid; tetracyclic diterpenoid	antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent
gemcitabine gemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.	8.41	1	1	organofluorine compound; pyrimidine 2'-deoxyribonucleoside	antimetabolite; antineoplastic agent; antiviral drug; DNA synthesis inhibitor; EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor; environmental contaminant; immunosuppressive agent; photosensitizing agent; prodrug; radiosensitizing agent; xenobiotic
docetaxel anhydrous Docetaxel: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.. docetaxel anhydrous : A tetracyclic diterpenoid that is paclitaxel with the N-benzyloxycarbonyl group replaced by N-tert-butoxycarbonyl, and the acetoxy group at position 10 replaced by a hydroxy group.	2.94	1	0	secondary alpha-hydroxy ketone; tetracyclic diterpenoid	antimalarial; antineoplastic agent; photosensitizing agent
diethylstilbestrol Diethylstilbestrol: A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed). diethylstilbestrol : An olefinic compound that is trans-hex-3-ene in which the hydrogens at positions 3 and 4 have been replaced by p-hydroxyphenyl groups.	2.07	1	0	olefinic compound; polyphenol	antifungal agent; antineoplastic agent; autophagy inducer; calcium channel blocker; carcinogenic agent; EC 1.1.1.146 (11beta-hydroxysteroid dehydrogenase) inhibitor; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor; endocrine disruptor; xenoestrogen
levoleucovorin Levoleucovorin: A folate analog consisting of the pharmacologically active isomer of LEUCOVORIN.. (6S)-5-formyltetrahydrofolic acid : The pharmacologically active (6S)-stereoisomer of 5-formyltetrahydrofolic acid.	3.41	1	1	5-formyltetrahydrofolic acid	antineoplastic agent; metabolite
cyclic gmp Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed). 3',5'-cyclic GMP : A 3',5'-cyclic purine nucleotide in which the purine nucleobase is specified as guanidine.	2.04	1	0	3',5'-cyclic purine nucleotide; guanyl ribonucleotide	Escherichia coli metabolite; human metabolite; mouse metabolite; plant metabolite; Saccharomyces cerevisiae metabolite
dacarbazine (E)-dacarbazine : A dacarbazine in which the N=N double bond adopts a trans-configuration.	3.44	1	1	dacarbazine

Condition	Indicated	Relationship Strength	Studies	Trials
Colorectal Cancer [description not available]	0	7.6	1	0
Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.	0	2.6	1	0
Benign Neoplasms [description not available]	0	5.85	6	4
Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	1	7.85	6	4
Angiogenesis, Pathologic [description not available]	0	5.84	8	1
Sarcoma, Epithelioid [description not available]	0	3.43	1	1
Sarcoma A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant.	1	10.43	1	1
Disease Exacerbation [description not available]	0	3.84	2	1
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	0	2.96	4	0
Cancer of Ovary [description not available]	0	2.46	2	0
Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.	0	2.46	2	0
Carcinoma, Epidermoid [description not available]	0	2.05	1	0
Cancer of Mouth [description not available]	0	2.05	1	0
Condition, Preneoplastic [description not available]	0	2.05	1	0
Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)	0	2.05	1	0
Mouth Neoplasms Tumors or cancer of the MOUTH.	0	2.05	1	0
Precancerous Conditions Pathological conditions that tend eventually to become malignant.	0	2.05	1	0
Benign Neoplasms, Brain [description not available]	0	3.83	2	1
Astrocytoma, Grade IV [description not available]	0	3.44	1	1
Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	1	5.83	2	1
Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.	0	8.44	1	1
Epithelial Neoplasms [description not available]	0	2.05	1	0
Adenoma, Prolactin-Secreting, Pituitary [description not available]	0	2.07	1	0
Carcinoma, Lewis Lung A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy.	0	2.94	1	0
Experimental Neoplasms [description not available]	0	2.94	1	0
Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)	0	7.03	1	0
Glial Cell Tumors [description not available]	0	2.03	1	0
Glioma Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)	0	7.03	1	0
Malignant Melanoma [description not available]	0	4.34	1	1
Cancer of Skin [description not available]	0	4.34	1	1
Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)	1	11.34	1	1
Skin Neoplasms Tumors or cancer of the SKIN.	0	4.34	1	1
Adenocarcinoma Of Kidney [description not available]	0	3.42	1	1
Cancer of Kidney [description not available]	0	3.42	1	1
Carcinoma, Renal Cell A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.	1	5.42	1	1
Kidney Neoplasms Tumors or cancers of the KIDNEY.	0	3.42	1	1
Bowel Diseases, Inflammatory [description not available]	0	2.04	1	0
Colitis Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.	0	2.04	1	0
Inflammatory Bowel Diseases Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.	0	2.04	1	0

abt-510

Description

Cross-References

Synonyms (18)

Research Excerpts

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Dosage Studied

Bioassays (2)

Research

Studies (27)

Market Indicators

Research Demand Index: 23.49

Study Types