ID: ALA342252

Max Phase: Preclinical

Molecular Formula: C38H64N12O8

Molecular Weight: 817.01

Molecule Type: Protein

Representations

Synonyms (1): Neurotensin(8-13)
Synonyms from Alternative Forms(1):

Canonical SMILES:  CC[C@@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)O

Standard InChI:  InChI=1S/C38H64N12O8/c1-5-22(4)30(34(55)48-28(36(57)58)19-21(2)3)49-32(53)27(20-23-12-14-24(51)15-13-23)47-33(54)29-11-8-18-50(29)35(56)26(10-7-17-45-38(42)43)46-31(52)25(39)9-6-16-44-37(40)41/h12-15,21-22,25-30,51H,5-11,16-20,39H2,1-4H3,(H,46,52)(H,47,54)(H,48,55)(H,49,53)(H,57,58)(H4,40,41,44)(H4,42,43,45)/t22-,25+,26+,27+,28+,29+,30+/m1/s1

Standard InChI Key:  DQDBCHHEIKQPJD-CSJNAZMVSA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Protein

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 817.01

Molecular Weight (Monoisotopic): 816.4970

AlogP: -1.10

#Rotatable Bonds: 24

Polar Surface Area: 344.06

Molecular Species: ZWITTERION

HBA: 10

HBD: 13

#RO5 Violations: 2

HBA (Lipinski): 20

HBD (Lipinski): 16

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 4.11

CX Basic pKa: 11.73

CX LogP: -4.71

CX LogD: -5.43

Aromatic Rings: 1

Heavy Atoms: 58

QED Weighted: 0.03

Np Likeness Score: 0.16

References

1. Wustrow D, Davis M, Akunne H, Corbin A, Wiley J, Wise L, Heffner T.  (1995)  Reduced amide bond neurotensin 813 mimetics with potent in vivo activity,  5  (9): [10.1016/0960-894X(95)00155-M]

2. González-Muñiz R, García-López MT, Gómez-Monterrey I, Herranz R, Jimeno ML, Suárez-Gea ML, Johansen NL, Madsen K, Thøgersen H, Suzdak P..  (1995)  Ketomethylene and (cyanomethylene)amino pseudopeptide analogues of the C-terminal hexapeptide of neurotensin.,  38  (6): [PMID:7699693] [10.1021/jm00006a021]

3. Cain GA, Christos TE, Johnson AL, Pottorf RS, Tam S, Schmidt WK.  (1993)  Identification of simpler analogs of neurotensin(913) which retain antinociceptive activity,  3  (8): [10.1016/S0960-894X(00)80059-1]

4. St-Pierre S, Lalonde JM, Gendreau M, Quirion R, Regoli D, Rioux F..  (1981)  Synthesis of peptides by the solid-phase method. 6. Neurotensin, fragments, and analogues.,  24  (4): [PMID:7265123] [10.1021/jm00136a004]

5. Kokko KP, Hadden MK, Orwig KS, Mazella J, Dix TA..  (2003)  In vitro analysis of stable, receptor-selective neurotensin[8-13] analogues.,  46  (19): [PMID:12954066] [10.1021/jm0300633]

6. Lundquist JT, Dix TA..  (1999)  Synthesis and human neurotensin receptor binding activities of neurotensin(8-13) analogues containing position 8 alpha-azido-N-alkylated derivatives of ornithine, lysine, and homolysine.,  42  (23): [PMID:10579853] [10.1021/jm9903444]

7. Henry JA, Horwell DC, Meecham KG, Rees DC.  (1993)  A structure-affinity study of the amino acid side-chains in neurotensin : N and C terminal deletions and Ala-scan,  3  (5): [10.1016/S0960-894X(00)80698-8]

8. Bittermann H, Einsiedel J, Hübner H, Gmeiner P..  (2004)  Evaluation of lactam-bridged neurotensin analogues adjusting psi(Pro10) close to the experimentally derived bioactive conformation of NT(8-13).,  47  (22): [PMID:15481995] [10.1021/jm049644y]

9. Einsiedel J, Hübner H, Hervet M, Härterich S, Koschatzky S, Gmeiner P..  (2008)  Peptide backbone modifications on the C-terminal hexapeptide of neurotensin.,  18  (6): [PMID:18276136] [10.1016/j.bmcl.2008.01.110]

10. Bredeloux P, Cavelier F, Dubuc I, Vivet B, Costentin J, Martinez J..  (2008)  Synthesis and biological effects of c(Lys-Lys-Pro-Tyr-Ile-Leu-Lys-Lys-Pro-Tyr-Ile-Leu) (JMV2012), a new analogue of neurotensin that crosses the blood-brain barrier.,  51  (6): [PMID:18321036] [10.1021/jm700925k]

11. Orwig KS, Lassetter MR, Hadden MK, Dix TA..  (2009)  Comparison of N-terminal modifications on neurotensin(8-13) analogues correlates peptide stability but not binding affinity with in vivo efficacy.,  52  (7): [PMID:19290594] [10.1021/jm801072v]

12. Härterich S, Koschatzky S, Einsiedel J, Gmeiner P..  (2008)  Novel insights into GPCR-peptide interactions: mutations in extracellular loop 1, ligand backbone methylations and molecular modeling of neurotensin receptor 1.,  16  (20): [PMID:18809332] [10.1016/j.bmc.2008.08.051]

13. Lang C, Maschauer S, Hübner H, Gmeiner P, Prante O..  (2013)  Synthesis and evaluation of a (18)F-labeled diarylpyrazole glycoconjugate for the imaging of NTS1-positive tumors.,  56  (22): [PMID:24160350] [10.1021/jm401491e]

14. Rivier JE, Lazarus LH, Perrin MH, Brown MR..  (1977)  Neurotensin analogues. Structure--activity relationships.,  20  (11): [PMID:915901] [10.1021/jm00221a011]

15. Thomas JB, Giddings AM, Wiethe RW, Olepu S, Warner KR, Sarret P, Gendron L, Longpre JM, Zhang Y, Runyon SP, Gilmour BP..  (2014)  Identification of 1-({[1-(4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane carboxylic acid as a selective nonpeptide neurotensin receptor type 2 compound.,  57  (12): [PMID:24856674] [10.1021/jm5003843]

Source

Source(1):

• Scientific Literature