NPASS Compound

Structure

CID201014 OpenBabel06191715592D 33 36 0 0 1 0 0 0 0 0999 V2000 1.3706 2.8482 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4183 2.8559 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3634 -3.8348 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8851 -2.3061 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2676 -2.1846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7160 0.0157 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4622 -0.7742 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4739 2.3357 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 -3.3452 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0312 -1.8000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7483 -3.0825 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3637 -0.7611 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1676 0.7840 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4695 1.3029 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1985 -3.8637 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3793 -1.7948 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2724 1.3011 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1074 -3.3482 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3951 -3.8623 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0469 -0.7664 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4394 0.7874 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4842 -2.3119 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1223 -2.3155 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1519 -0.2497 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.4553 -0.2459 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.3635 0.7857 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.3036 -3.3471 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2442 -2.2892 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2763 2.2973 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9646 -3.8559 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8466 -3.0818 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1557 -0.7595 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 8 1 0 0 0 0 2 8 1 0 0 0 0 5 11 1 0 0 0 0 6 13 2 0 0 0 0 6 32 1 0 0 0 0 7 12 2 0 0 0 0 7 33 1 0 0 0 0 9 3 1 1 0 0 0 9 19 1 0 0 0 0 9 22 1 0 0 0 0 10 4 1 1 0 0 0 10 20 1 0 0 0 0 10 23 1 0 0 0 0 11 15 2 0 0 0 0 11 31 1 0 0 0 0 12 16 1 0 0 0 0 12 25 1 0 0 0 0 13 17 1 0 0 0 0 13 24 1 0 0 0 0 14 8 1 1 0 0 0 14 21 1 0 0 0 0 14 26 1 0 0 0 0 15 18 1 0 0 0 0 15 27 1 0 0 0 0 16 22 2 3 0 0 0 16 28 1 0 0 0 0 17 26 2 3 0 0 0 17 29 1 0 0 0 0 18 23 2 3 0 0 0 18 30 1 0 0 0 0 19 27 2 0 0 0 0 19 31 1 0 0 0 0 20 24 2 0 0 0 0 20 32 1 0 0 0 0 21 25 2 0 0 0 0 21 33 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	488.13
Volume:	451.978
LogP:	4.278
LogD:	3.105
LogS:	-5.577
# Rotatable Bonds:	1
TPSA:	139.11
# H-Bond Aceptor:	10
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.477
Synthetic Accessibility Score:	6.008
Fsp3:	0.429
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-5.106
MDCK Permeability:	1.4297028428700287e-05
Pgp-inhibitor:	0.864
Pgp-substrate:	0.997
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.106

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008
Plasma Protein Binding (PPB):	97.24190521240234%
Volume Distribution (VD):	1.306
Pgp-substrate:	2.672541618347168%

ADMET: Metabolism

CYP1A2-inhibitor:	0.576
CYP1A2-substrate:	0.387
CYP2C19-inhibitor:	0.594
CYP2C19-substrate:	0.061
CYP2C9-inhibitor:	0.855
CYP2C9-substrate:	0.036
CYP2D6-inhibitor:	0.007
CYP2D6-substrate:	0.149
CYP3A4-inhibitor:	0.655
CYP3A4-substrate:	0.291

ADMET: Excretion

Clearance (CL):	1.326
Half-life (T1/2):	0.078

ADMET: Toxicity

hERG Blockers:	0.012
Human Hepatotoxicity (H-HT):	0.954
Drug-inuced Liver Injury (DILI):	0.987
AMES Toxicity:	0.012
Rat Oral Acute Toxicity:	0.007
Maximum Recommended Daily Dose:	0.879
Skin Sensitization:	0.021
Carcinogencity:	0.036
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.77

Download Data

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

Natural Product: NPC201014

Natural Product ID:	NPC201014
*Common Name:**	Venturamide A
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	OJMSNONHTSXZKM-GPCCPHFNSA-N
Standard InCHI:	InChI=1S/C21H24N6O4S2/c1-8(2)14-21-25-12(7-33-21)16(28)22-9(3)19-27-15(11(5)31-19)18(30)23-10(4)20-24-13(6-32-20)17(29)26-14/h6-10,14H,1-5H3,(H,22,28)(H,23,30)(H,26,29)/t9-,10-,14-/m1/s1
SMILES:	CC(C)[C@@H]1c2nc(cs2)C(=N[C@H](C)c2nc(c(C)o2)C(=N[C@H](C)c2nc(cs2)C(=N1)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL375099
PubChem CID:	11225555
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000064] Macrolactams

*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
NPO31273	Oscillatoria sp.	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[16930043]
NPO31273	Oscillatoria sp.	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[17328572]
NPO31273	Oscillatoria sp.	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[20525864]
NPO31273	Oscillatoria sp.	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[21473610]
NPO31273	Oscillatoria sp.	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[21999614]

☑ 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	7

Activity Type	# Activity
Cell Line	3
Organism	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT189	Cell Line	Vero	Chlorocebus aethiops	IC50	=	86000.0	nM	PMID[486710]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	13100.0	nM	PMID[486710]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	8200.0	nM	PMID[486711]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	8200.0	nM	PMID[486710]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	14600.0	nM	PMID[486710]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	>	20000.0	nM	PMID[486710]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	13100.0	nM	PMID[486711]

☑ 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 NPC201014 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	440
0.1-0.2	21407
0.2-0.3	16550
0.3-0.4	3960
0.4-0.5	227
0.5-0.6	86
0.6-0.7	16
0.7-0.8	1
0.8-0.85	2
0.85-0.9	0
0.9-0.95	1
0.95-1	7

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC110129
0.9866	High Similarity	NPC222391
0.9796	High Similarity	NPC217981
0.9671	High Similarity	NPC34319
0.9542	High Similarity	NPC256912
0.8581	High Similarity	NPC50274
0.8428	Intermediate Similarity	NPC237219
0.7617	Intermediate Similarity	NPC235866
0.7124	Intermediate Similarity	NPC51692
0.6975	Remote Similarity	NPC103268
0.6943	Remote Similarity	NPC89592
0.6908	Remote Similarity	NPC214375
0.677	Remote Similarity	NPC74917
0.6728	Remote Similarity	NPC120917
0.671	Remote Similarity	NPC135558
0.6627	Remote Similarity	NPC475390
0.6582	Remote Similarity	NPC267605
0.6465	Remote Similarity	NPC315872
0.6304	Remote Similarity	NPC164006
0.6138	Remote Similarity	NPC132662
0.5943	Remote Similarity	NPC469801
0.5888	Remote Similarity	NPC49195
0.5817	Remote Similarity	NPC315061
0.58	Remote Similarity	NPC315411
0.5798	Remote Similarity	NPC475554
0.5753	Remote Similarity	NPC216720
0.5729	Remote Similarity	NPC134480
0.5722	Remote Similarity	NPC161242
0.5722	Remote Similarity	NPC210424
0.5722	Remote Similarity	NPC476080
0.5722	Remote Similarity	NPC475534
0.5707	Remote Similarity	NPC96016
0.5699	Remote Similarity	NPC473704
0.5692	Remote Similarity	NPC475330
0.5663	Remote Similarity	NPC263485
0.5663	Remote Similarity	NPC229160
0.5663	Remote Similarity	NPC174652
0.5663	Remote Similarity	NPC25316

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 NPC201014 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	176
0.1-0.2	1781
0.2-0.3	4149
0.3-0.4	2728
0.4-0.5	277
0.5-0.6	38
0.6-0.7	1
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
0.6465	Remote Similarity	NPD6444	Clinical (unspecified phase)
0.6129	Remote Similarity	NPD2623	Phase 1
0.5805	Remote Similarity	NPD7896	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