Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C96H129N21O20 |
| Molecular Weight | 1897.1802 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 16 / 16 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@](C)(O)[C@@H](NC(=O)[C@@H](CO)NC(=O)[C@H]1CCCN1C(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@@H](CC3=CC=CC=C3)NC(=O)[C@H](NC(=O)[C@@H](CC4=CNC5=C4C=CC=C5)NC(=O)[C@H](N)CC6=CNC7=C6C=CC=C7)[C@]([H])(C)O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC8=CNC9=C8C=CC=C9)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCNC(N)=N)C(=O)N[C@H](CCCCN)C(O)=O
InChI
InChIKey=FNQVICDIQNFNHD-NOQIVBDNSA-N
InChI=1S/C96H129N21O20/c1-52(2)41-71(85(126)110-74(46-59-49-103-66-31-17-14-28-62(59)66)88(129)106-69(36-37-79(121)122)84(125)105-68(34-21-39-101-96(99)100)83(124)107-70(95(136)137)33-19-20-38-97)111-92(133)81(55(6)120)116-90(131)77(51-118)114-91(132)78-35-22-40-117(78)94(135)76(42-53(3)4)113-87(128)72(43-56-23-9-7-10-24-56)109-86(127)73(44-57-25-11-8-12-26-57)112-93(134)80(54(5)119)115-89(130)75(47-60-50-104-67-32-18-15-29-63(60)67)108-82(123)64(98)45-58-48-102-65-30-16-13-27-61(58)65/h7-18,23-32,48-50,52-55,64,68-78,80-81,102-104,118-120H,19-22,33-47,51,97-98H2,1-6H3,(H,105,125)(H,106,129)(H,107,124)(H,108,123)(H,109,127)(H,110,126)(H,111,133)(H,112,134)(H,113,128)(H,114,132)(H,115,130)(H,116,131)(H,121,122)(H,136,137)(H4,99,100,101)/t54-,55-,64+,68+,69+,70+,71+,72+,73+,74+,75+,76+,77+,78+,80+,81+/m0/s1
| Molecular Formula | C96H129N21O20 |
| Molecular Weight | 1897.1802 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 16 / 16 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Nerofe, the flagship compound of Immune System Key Ltd, is a 14 amino acid modifed form of a novel human hormone-peptide, which was found to be a native ligand of the ST2 receptor and plays a pivotal role in immune system response. Nerofe is a derivative of the human hormone-peptide Tumor-Cells Apoptosis Factor (TCApF). TCApF binds to the T1/ST2 receptor and activates caspases 8, 9 and 3 mediated apoptosis, together with activation of JNKinase and p38 MAPKinase. Application of TCApF to cells induced apoptosis in acute myeloid leukemia proliferating cells (U937 premeyloid cells), in human breast carcinoma (MCF7), human glioblastoma, human neuroblastoma, human prostate cancer and human lung cancer proliferating cells. In contrast, TCApF was unable to induce apoptosis in non-proliferating cells. The selectivity of TCApF-induced apoptosis is related to the level of T1/ST2 receptor expression. Nerofe was granted by the FDA with orphan drug status for AML treatment and currently is in phase IIa development stage. Immune System Key Ltd holds 3 worldwide patents on the molecule and applications.
Originator
Approval Year
Sample Use Guides
Acute Myelogenous Leukemia; Myelodysplastic Syndromes:
48mg/m2 IV Nerofe - three times a week
96mg/m2 IV Nerofe - three times a week
48mg/m2 IV Nerofe + Doxorubicin 10mg/m2 - once a week
Route of Administration:
Intravenous
In MDA-MB-231 cells treated with Nerofe (25 or 50 ug/ml for 24 h followed by an additional dose of 25 or 50 ug/ml for a further 72 h), the Golgi apparatus structure was diffused, compared with controls (no Nerofe treatment). Apoptosis was observed in PANC-1, OV-90 and MDA-MB-231 cells treated with increasing concentrations of Nerofe (10-50 ug/ml) for 24 h followed by another dTCApFs dose for 72 h.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 12:03:29 GMT 2023
by
admin
on
Sat Dec 16 12:03:29 GMT 2023
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| Record UNII |
SR717JCM7M
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| Record Status |
Validated (UNII)
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| Record Version |
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FDA ORPHAN DRUG |
331210
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SR717JCM7M
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1311294-45-7
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NO STRUCTURE GIVEN | |||
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145722610
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C103193
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DB14786
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2120397-85-3
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| Related Record | Type | Details | ||
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TARGET -> ACTIVATOR |
| Related Record | Type | Details | ||
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ACTIVE MOIETY |
Nerofe administered at doses up to 96 mg/m2 is safe, welltolerated
and demonstrates interesting anti-angiogenic activity
in combination with increased immune cytokines. Tumor T1/ST2
expression may be a biomarker for sensitivity to Nerofe.
Dose-escalation continues in this trial.
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ACTIVE MOIETY |
Official Title: A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Intravenously Administered Nerofe in Subjects With Advanced Malignancies
Purpose: This study will be the first to test the anti-cancer peptide Nerofe in humans. It will evaluate the safety, pharmacokinetic behavior, and pharmacodynamic and clinical effects of Nerofe given intravenously every other day to patients with advanced malignant disease.
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ACTIVE MOIETY |
Immunohistochemical studies localize Tumor-Cells Apoptosis Factor (TCApF) to the medulla and Hassal's corpuscles of the thymus gland, which are responsible for negative selection. Treatment of mice with induced AML terminates the cancer development and completely eliminates metastatic cell colonies from the bone marrow and the spleen that reduces probability of the cancer return. We find that TCApF binds to the T1/ST2 receptor and activates caspases 8, 9 and 3 mediated apoptosis, together with activation of JNKinase and p38 MAPKinase. Application of TCApF to cells induced apoptosis in acute myeloid leukemia proliferating cells (U937 premeyloid cells), in human breast carcinoma (MCF7), human glioblastoma, human neuroblastoma, human prostate cancer and human lung cancer proliferating cells. In contrast, TCApF was unable to induce apoptosis in non-proliferating cells.
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