NPASS Compound

Structure

NPC82919 OpenBabel07101718312D 34 37 0 0 1 0 0 0 0 0999 V2000 0.2211 2.9484 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6513 2.9032 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1963 2.8351 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8666 1.8995 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0361 2.7057 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1668 1.3404 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3847 2.3124 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5446 2.5787 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2448 0.7106 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3235 2.3825 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7862 2.5233 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7768 2.2138 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0900 0.0952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4748 1.9773 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1519 2.5037 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8615 1.7896 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7234 -0.4227 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4695 1.5448 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5675 2.2564 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7872 1.3636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.9090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1944 -0.7733 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3083 1.1434 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7872 -1.3636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1533 1.2381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8092 1.7297 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5745 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6235 0.6394 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1119 1.8146 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7872 0.4545 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1924 0.6047 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5745 -0.9090 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 1.0130 0.8274 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 1 2 2 0 0 0 0 1 3 1 0 0 0 0 2 5 1 0 0 0 0 3 8 1 0 0 0 0 4 6 1 0 0 0 0 4 7 1 0 0 0 0 5 10 1 0 0 0 0 6 9 1 0 0 0 0 7 11 1 0 0 0 0 8 12 1 0 0 0 0 9 13 2 0 0 0 0 10 14 2 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 19 1 0 0 0 0 16 20 1 0 0 0 0 17 22 1 0 0 0 0 18 23 1 0 0 0 0 21 24 1 0 0 0 0 22 33 1 0 0 0 0 23 34 1 0 0 0 0 24 33 1 0 0 0 0 25 29 1 0 0 0 0 26 29 1 0 0 0 0 26 34 1 0 0 0 0 27 30 1 0 0 0 0 27 33 1 0 0 0 0 28 31 1 0 0 0 0 28 34 1 0 0 0 0 29 19 1 1 0 0 0 30 20 1 6 0 0 0 30 32 1 0 0 0 0 31 25 1 1 0 0 0 31 32 1 0 0 0 0 32 21 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	466.43
Volume:	541.886
LogP:	5.508
LogD:	4.793
LogS:	-2.829
# 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:	0.333
Synthetic Accessibility Score:	6.159
Fsp3:	0.812
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:	-5.07
MDCK Permeability:	4.0006179915508255e-05
Pgp-inhibitor:	0.002
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.521
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.052
Plasma Protein Binding (PPB):	98.25608825683594%
Volume Distribution (VD):	2.016
Pgp-substrate:	2.8353452682495117%

ADMET: Metabolism

CYP1A2-inhibitor:	0.053
CYP1A2-substrate:	0.736
CYP2C19-inhibitor:	0.208
CYP2C19-substrate:	0.165
CYP2C9-inhibitor:	0.026
CYP2C9-substrate:	0.082
CYP2D6-inhibitor:	0.993
CYP2D6-substrate:	0.958
CYP3A4-inhibitor:	0.134
CYP3A4-substrate:	0.368

ADMET: Excretion

Clearance (CL):	3.944
Half-life (T1/2):	0.815

ADMET: Toxicity

hERG Blockers:	0.705
Human Hepatotoxicity (H-HT):	0.918
Drug-inuced Liver Injury (DILI):	0.178
AMES Toxicity:	0.448
Rat Oral Acute Toxicity:	0.028
Maximum Recommended Daily Dose:	0.185
Skin Sensitization:	0.98
Carcinogencity:	0.259
Eye Corrosion:	0.043
Eye Irritation:	0.083
Respiratory Toxicity:	0.885

Download Data

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

Natural Product: NPC82919

Natural Product ID:	NPC82919
*Common Name:**	Haliclonacyclamine F
IUPAC Name:	n.a.
Synonyms:	Haliclonacyclamine F
Standard InCHIKey:	XKZBXMNTTBNTDQ-UYXCOTLJSA-N
Standard InCHI:	InChI=1S/C32H54N2/c1-2-5-10-14-18-23-34-26-29-19-15-11-7-4-6-9-13-17-22-33-24-21-32(31(25-29)28-34)30(27-33)20-16-12-8-3-1/h1-2,9-10,13-14,29-32H,3-8,11-12,15-28H2/b2-1-,13-9-,14-10-/t29-,30+,31+,32+/m1/s1
SMILES:	C1CCCC[C@H]2CN3CC/C=CC/C=CCCCCC[C@H]4CN(CC/C=CC1)CC[C@@H]4[C@@H](C2)C3
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL222823
PubChem CID:	16215158
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
NPO6365	Pachychalina alcaloidifera	Species	Niphatidae	Eukaryota	n.a.	Brazilian	n.a.	PMID[17346073]
NPO6365	Pachychalina alcaloidifera	Species	Niphatidae	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
Others	4

Activity Type	# Activity
Cell Line	3
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT399	Cell Line	SF-295	Homo sapiens	Activity	=	4.5	ug ml-1	PMID[545386]
NPT180	Cell Line	HCT-8	Homo sapiens	Activity	=	8.6	ug ml-1	PMID[545386]
NPT116	Cell Line	HL-60	Homo sapiens	Activity	=	2.2	ug ml-1	PMID[545386]
NPT27	Others	Unspecified		Activity	=	1.0	ug ml-1	PMID[545386]

☑ 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 NPC82919 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	288
0.1-0.2	7170
0.2-0.3	23363
0.3-0.4	10136
0.4-0.5	1504
0.5-0.6	182
0.6-0.7	42
0.7-0.8	9
0.8-0.85	1
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	NPC231129
0.8689	High Similarity	NPC476559
0.7656	Intermediate Similarity	NPC472544
0.7639	Intermediate Similarity	NPC473695
0.7639	Intermediate Similarity	NPC473446
0.7143	Intermediate Similarity	NPC472543
0.6974	Remote Similarity	NPC476560
0.68	Remote Similarity	NPC308050
0.6623	Remote Similarity	NPC127430
0.6623	Remote Similarity	NPC120699
0.6622	Remote Similarity	NPC476904
0.6575	Remote Similarity	NPC265789
0.6575	Remote Similarity	NPC21773
0.6447	Remote Similarity	NPC7214
0.6447	Remote Similarity	NPC259989
0.6447	Remote Similarity	NPC174803
0.6329	Remote Similarity	NPC12035
0.6316	Remote Similarity	NPC125828
0.6296	Remote Similarity	NPC171639
0.625	Remote Similarity	NPC474122
0.622	Remote Similarity	NPC135639
0.622	Remote Similarity	NPC61321
0.622	Remote Similarity	NPC78058
0.622	Remote Similarity	NPC234822
0.622	Remote Similarity	NPC207048
0.622	Remote Similarity	NPC143344
0.6094	Remote Similarity	NPC243635
0.6094	Remote Similarity	NPC151004
0.6094	Remote Similarity	NPC228980
0.6056	Remote Similarity	NPC206660
0.6049	Remote Similarity	NPC118329
0.6049	Remote Similarity	NPC152039
0.6032	Remote Similarity	NPC201713
0.6029	Remote Similarity	NPC472830
0.6	Remote Similarity	NPC211322
0.6	Remote Similarity	NPC219621
0.5976	Remote Similarity	NPC215474
0.5897	Remote Similarity	NPC63284
0.5889	Remote Similarity	NPC119225
0.5889	Remote Similarity	NPC471635
0.5889	Remote Similarity	NPC25033
0.5889	Remote Similarity	NPC476261
0.5889	Remote Similarity	NPC470382
0.5857	Remote Similarity	NPC311809
0.5857	Remote Similarity	NPC317778
0.5854	Remote Similarity	NPC329782
0.5833	Remote Similarity	NPC57163
0.5833	Remote Similarity	NPC116881
0.5833	Remote Similarity	NPC471867
0.5833	Remote Similarity	NPC473959
0.5823	Remote Similarity	NPC320667
0.5823	Remote Similarity	NPC214125
0.5802	Remote Similarity	NPC268580
0.5789	Remote Similarity	NPC473254
0.5783	Remote Similarity	NPC472312
0.573	Remote Similarity	NPC145707
0.5714	Remote Similarity	NPC124851
0.5714	Remote Similarity	NPC472827
0.5698	Remote Similarity	NPC157479
0.5694	Remote Similarity	NPC145715
0.5676	Remote Similarity	NPC37792
0.5667	Remote Similarity	NPC177470
0.5652	Remote Similarity	NPC173815
0.5652	Remote Similarity	NPC470370
0.5652	Remote Similarity	NPC470369
0.5634	Remote Similarity	NPC42477
0.5625	Remote Similarity	NPC17518
0.5625	Remote Similarity	NPC17810
0.5625	Remote Similarity	NPC106990
0.5625	Remote Similarity	NPC22765

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 NPC82919 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	191
0.1-0.2	1404
0.2-0.3	4916
0.3-0.4	2100
0.4-0.5	467
0.5-0.6	69
0.6-0.7	3
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
0.6667	Remote Similarity	NPD3727	Discontinued
0.6406	Remote Similarity	NPD3711	Phase 3
0.6406	Remote Similarity	NPD3712	Phase 3
0.6351	Remote Similarity	NPD5365	Phase 2
0.6094	Remote Similarity	NPD1822	Approved
0.6094	Remote Similarity	NPD1821	Approved
0.6094	Remote Similarity	NPD1823	Approved
0.5938	Remote Similarity	NPD5793	Discontinued
0.5854	Remote Similarity	NPD4027	Approved
0.5854	Remote Similarity	NPD4026	Approved
0.5846	Remote Similarity	NPD3721	Approved
0.5846	Remote Similarity	NPD3722	Approved
0.5783	Remote Similarity	NPD4701	Clinical (unspecified phase)
0.5783	Remote Similarity	NPD4170	Approved
0.5783	Remote Similarity	NPD4169	Approved
0.5781	Remote Similarity	NPD4834	Discontinued
0.5698	Remote Similarity	NPD4409	Approved
0.5698	Remote Similarity	NPD4406	Approved
0.5698	Remote Similarity	NPD4636	Approved
0.5663	Remote Similarity	NPD3035	Approved
0.5625	Remote Similarity	NPD8262	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