NPASS Compound

Structure

NPC231129 OpenBabel07101719512D 32 35 0 0 1 0 0 0 0 0999 V2000 -2.8583 1.8940 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0373 2.6878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1576 1.3365 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4741 2.6743 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3778 2.3056 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3672 2.5224 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2354 0.7086 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8677 2.4844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7810 2.5159 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6695 2.2067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0810 0.0949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1501 2.1508 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1485 2.4964 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8173 1.7954 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7155 -0.4215 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2723 1.7312 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5659 2.2498 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7850 1.3596 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.9064 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1880 -0.7710 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2132 1.2981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7850 -1.3596 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1529 1.2345 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7565 1.7656 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5699 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6219 0.6806 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1116 1.8093 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7850 0.4532 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1918 0.6030 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5699 -0.9064 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 0.9832 0.9265 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 1 3 2 0 0 0 0 1 5 1 0 0 0 0 2 4 2 0 0 0 0 2 6 1 0 0 0 0 3 7 1 0 0 0 0 4 8 1 0 0 0 0 5 9 1 0 0 0 0 6 10 1 0 0 0 0 7 11 1 0 0 0 0 8 12 1 0 0 0 0 9 13 1 0 0 0 0 10 14 1 0 0 0 0 11 15 1 0 0 0 0 12 16 1 0 0 0 0 13 17 1 0 0 0 0 14 18 1 0 0 0 0 15 20 1 0 0 0 0 16 21 1 0 0 0 0 19 22 1 0 0 0 0 20 31 1 0 0 0 0 21 32 1 0 0 0 0 22 31 1 0 0 0 0 23 27 1 0 0 0 0 24 27 1 0 0 0 0 24 32 1 0 0 0 0 25 28 1 0 0 0 0 25 31 1 0 0 0 0 26 29 1 0 0 0 0 26 32 1 0 0 0 0 27 17 1 1 0 0 0 28 18 1 6 0 0 0 28 30 1 0 0 0 0 29 23 1 1 0 0 0 29 30 1 0 0 0 0 30 19 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	440.41
Volume:	509.931
LogP:	6.039
LogD:	4.853
LogS:	-3.218
# Rotatable Bonds:	0
TPSA:	6.48
# H-Bond Aceptor:	2
# H-Bond Donor:	0
# Rings:	5
# Heavy Atoms:	2

MedChem Properties

QED Drug-Likeness Score:	0.361
Synthetic Accessibility Score:	5.907
Fsp3:	0.867
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.055
MDCK Permeability:	2.859836968127638e-05
Pgp-inhibitor:	0.011
Pgp-substrate:	0.007
Human Intestinal Absorption (HIA):	0.397
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.02
Plasma Protein Binding (PPB):	97.86713409423828%
Volume Distribution (VD):	1.338
Pgp-substrate:	2.507354259490967%

ADMET: Metabolism

CYP1A2-inhibitor:	0.054
CYP1A2-substrate:	0.687
CYP2C19-inhibitor:	0.169
CYP2C19-substrate:	0.134
CYP2C9-inhibitor:	0.017
CYP2C9-substrate:	0.052
CYP2D6-inhibitor:	0.994
CYP2D6-substrate:	0.95
CYP3A4-inhibitor:	0.114
CYP3A4-substrate:	0.335

ADMET: Excretion

Clearance (CL):	4.493
Half-life (T1/2):	0.69

ADMET: Toxicity

hERG Blockers:	0.936
Human Hepatotoxicity (H-HT):	0.912
Drug-inuced Liver Injury (DILI):	0.235
AMES Toxicity:	0.058
Rat Oral Acute Toxicity:	0.043
Maximum Recommended Daily Dose:	0.206
Skin Sensitization:	0.978
Carcinogencity:	0.06
Eye Corrosion:	0.334
Eye Irritation:	0.249
Respiratory Toxicity:	0.912

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC231129

Natural Product ID:	NPC231129
*Common Name:**	Neopetrosiamine A
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	VDKGIMKVQUXITF-MYWASIGGSA-N
Standard InCHI:	InChI=1S/C30H52N2/c1-3-7-11-15-20-31-22-19-30-28(25-31)18-14-10-6-2-4-8-12-16-21-32-24-27(17-13-9-5-1)23-29(30)26-32/h1-4,27-30H,5-26H2/b3-1-,4-2-/t27-,28+,29+,30-/m1/s1
SMILES:	C1=CCCCCN2CC[C@@H]3[C@@H](CCCC/C=CCCCCN4C[C@H](CCCC1)C[C@H]3C4)C2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1258043
PubChem CID:	49765082
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000195] Piperidines

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO22865	Neopetrosia proxima	Species	Petrosiidae	Eukaryota	n.a.	Caribbean sea	n.a.	PMID[20727745]
NPO22865	Neopetrosia proxima	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21341726]
NPO22865	Neopetrosia proxima	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	5
MIC	1

Activity Type	# Activity
Cell Line	4
Organism	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT375	Cell Line	Malme-3M	Homo sapiens	IC50	=	1500.0	nM	PMID[482826]
NPT404	Cell Line	CCRF-CEM	Homo sapiens	IC50	=	2000.0	nM	PMID[482826]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	3500.0	nM	PMID[482826]
NPT189	Cell Line	Vero	Chlorocebus aethiops	IC50	=	42.4	ug.mL-1	PMID[482826]
NPT790	Organism	Mycobacterium tuberculosis H37Rv	Mycobacterium tuberculosis H37Rv	MIC	=	7.5	ug.mL-1	PMID[482826]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	2300.0	nM	PMID[482826]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC231129 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	283
0.1-0.2	6892
0.2-0.3	23643
0.3-0.4	10018
0.4-0.5	1605
0.5-0.6	194
0.6-0.7	51
0.7-0.8	7
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9818	High Similarity	NPC82919
0.8525	High Similarity	NPC476559
0.7778	Intermediate Similarity	NPC472544
0.75	Intermediate Similarity	NPC473446
0.75	Intermediate Similarity	NPC473695
0.7246	Intermediate Similarity	NPC472543
0.6892	Remote Similarity	NPC308050
0.6842	Remote Similarity	NPC476560
0.6711	Remote Similarity	NPC120699
0.6711	Remote Similarity	NPC127430
0.6667	Remote Similarity	NPC265789
0.6667	Remote Similarity	NPC21773
0.6533	Remote Similarity	NPC259989
0.6533	Remote Similarity	NPC174803
0.6533	Remote Similarity	NPC7214
0.6486	Remote Similarity	NPC476904
0.641	Remote Similarity	NPC12035
0.64	Remote Similarity	NPC125828
0.6375	Remote Similarity	NPC171639
0.6329	Remote Similarity	NPC474122
0.6296	Remote Similarity	NPC135639
0.6296	Remote Similarity	NPC143344
0.6296	Remote Similarity	NPC61321
0.6296	Remote Similarity	NPC78058
0.6296	Remote Similarity	NPC207048
0.6296	Remote Similarity	NPC234822
0.619	Remote Similarity	NPC228980
0.619	Remote Similarity	NPC243635
0.619	Remote Similarity	NPC151004
0.6143	Remote Similarity	NPC206660
0.6129	Remote Similarity	NPC201713
0.6125	Remote Similarity	NPC118329
0.6125	Remote Similarity	NPC152039
0.6119	Remote Similarity	NPC472830
0.6087	Remote Similarity	NPC219621
0.6076	Remote Similarity	NPC211322
0.6049	Remote Similarity	NPC215474
0.5974	Remote Similarity	NPC63284
0.5942	Remote Similarity	NPC317778
0.5942	Remote Similarity	NPC311809
0.5926	Remote Similarity	NPC329782
0.5915	Remote Similarity	NPC473959
0.5904	Remote Similarity	NPC471867
0.5904	Remote Similarity	NPC57163
0.5904	Remote Similarity	NPC116881
0.5897	Remote Similarity	NPC320667
0.5897	Remote Similarity	NPC214125
0.5875	Remote Similarity	NPC268580
0.5854	Remote Similarity	NPC472312
0.5806	Remote Similarity	NPC124851
0.5797	Remote Similarity	NPC472827
0.5795	Remote Similarity	NPC145707
0.5778	Remote Similarity	NPC470382
0.5778	Remote Similarity	NPC471635
0.5778	Remote Similarity	NPC119225
0.5778	Remote Similarity	NPC476261
0.5778	Remote Similarity	NPC25033
0.5775	Remote Similarity	NPC145715
0.5765	Remote Similarity	NPC157479
0.5763	Remote Similarity	NPC177470
0.5753	Remote Similarity	NPC37792
0.5735	Remote Similarity	NPC470370
0.5735	Remote Similarity	NPC470369
0.5735	Remote Similarity	NPC173815
0.5714	Remote Similarity	NPC17518
0.5714	Remote Similarity	NPC106990
0.5714	Remote Similarity	NPC42477
0.5714	Remote Similarity	NPC22765
0.5684	Remote Similarity	NPC473254
0.5663	Remote Similarity	NPC255430
0.5652	Remote Similarity	NPC324944
0.5647	Remote Similarity	NPC147513
0.5647	Remote Similarity	NPC76283
0.5645	Remote Similarity	NPC323445
0.5625	Remote Similarity	NPC244256
0.5625	Remote Similarity	NPC86452
0.5606	Remote Similarity	NPC476679

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC231129 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	189
0.1-0.2	1354
0.2-0.3	4886
0.3-0.4	2160
0.4-0.5	479
0.5-0.6	76
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6774	Remote Similarity	NPD3727	Discontinued
0.6508	Remote Similarity	NPD3712	Phase 3
0.6508	Remote Similarity	NPD3711	Phase 3
0.6438	Remote Similarity	NPD5365	Phase 2
0.619	Remote Similarity	NPD1823	Approved
0.619	Remote Similarity	NPD1821	Approved
0.619	Remote Similarity	NPD1822	Approved
0.6032	Remote Similarity	NPD5793	Discontinued
0.5938	Remote Similarity	NPD3721	Approved
0.5938	Remote Similarity	NPD3722	Approved
0.5926	Remote Similarity	NPD4027	Approved
0.5926	Remote Similarity	NPD4026	Approved
0.5873	Remote Similarity	NPD4834	Discontinued
0.5854	Remote Similarity	NPD4701	Clinical (unspecified phase)
0.5854	Remote Similarity	NPD4170	Approved
0.5854	Remote Similarity	NPD4169	Approved
0.5765	Remote Similarity	NPD4406	Approved
0.5765	Remote Similarity	NPD4409	Approved
0.5765	Remote Similarity	NPD4636	Approved
0.5732	Remote Similarity	NPD3035	Approved
0.5632	Remote Similarity	NPD5675	Discontinued
0.5625	Remote Similarity	NPD4147	Approved
0.5625	Remote Similarity	NPD4144	Approved

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data