NPASS Compound

Structure

CID135558 OpenBabel06191715492D 37 40 0 0 1 0 0 0 0 0999 V2000 -5.3957 3.2092 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4159 1.4293 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8961 2.9333 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9164 4.7132 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3738 -2.8255 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4053 -2.8458 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2546 2.1722 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7005 -0.0156 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4592 0.7695 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8920 2.3134 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3924 3.8291 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4784 -2.3221 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7382 3.0647 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1493 -0.7794 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3552 0.7566 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0079 1.7894 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4966 3.3254 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4667 -1.2949 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1855 3.8412 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2594 -1.2935 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3707 1.7842 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0890 3.3287 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0234 0.7618 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3932 3.8395 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4368 -0.7824 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1335 0.2477 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.4517 0.2442 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.4811 2.2978 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.1048 2.3016 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.3563 -0.7813 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.2968 3.3270 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2634 -2.2900 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2375 2.2760 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9463 3.8369 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1375 0.7550 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8420 3.0638 0.0000 O 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 10 1 0 0 0 0 2 10 1 0 0 0 0 3 11 1 0 0 0 0 4 11 1 0 0 0 0 5 12 1 0 0 0 0 6 12 1 0 0 0 0 8 35 1 0 0 0 0 9 15 2 0 0 0 0 9 37 1 0 0 0 0 13 7 1 6 0 0 0 13 19 1 0 0 0 0 13 36 1 0 0 0 0 14 8 1 6 0 0 0 14 20 1 0 0 0 0 14 26 1 0 0 0 0 15 21 1 0 0 0 0 15 27 1 0 0 0 0 16 10 1 6 0 0 0 16 23 1 0 0 0 0 16 29 1 0 0 0 0 17 11 1 6 0 0 0 17 24 1 0 0 0 0 17 28 1 0 0 0 0 18 12 1 6 0 0 0 18 25 1 0 0 0 0 18 30 1 0 0 0 0 19 22 1 1 0 0 0 19 31 1 0 0 0 0 20 30 2 3 0 0 0 20 32 1 0 0 0 0 21 28 2 3 0 0 0 21 33 1 0 0 0 0 22 29 2 3 0 0 0 22 34 1 0 0 0 0 23 26 2 0 0 0 0 23 35 1 0 0 0 0 24 31 2 0 0 0 0 24 36 1 0 0 0 0 25 27 2 0 0 0 0 25 37 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	532.25
Volume:	516.716
LogP:	2.852
LogD:	2.239
LogS:	-2.527
# Rotatable Bonds:	3
TPSA:	157.95
# H-Bond Aceptor:	11
# H-Bond Donor:	4
# Rings:	4
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.456
Synthetic Accessibility Score:	7.215
Fsp3:	0.64
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.582
MDCK Permeability:	3.479438237263821e-05
Pgp-inhibitor:	0.0
Pgp-substrate:	0.997
Human Intestinal Absorption (HIA):	0.019
20% Bioavailability (F20%):	0.667
30% Bioavailability (F30%):	0.904

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.818
Plasma Protein Binding (PPB):	58.2469482421875%
Volume Distribution (VD):	4.602
Pgp-substrate:	21.34479522705078%

ADMET: Metabolism

CYP1A2-inhibitor:	0.048
CYP1A2-substrate:	0.03
CYP2C19-inhibitor:	0.047
CYP2C19-substrate:	0.069
CYP2C9-inhibitor:	0.157
CYP2C9-substrate:	0.033
CYP2D6-inhibitor:	0.013
CYP2D6-substrate:	0.069
CYP3A4-inhibitor:	0.054
CYP3A4-substrate:	0.656

ADMET: Excretion

Clearance (CL):	1.954
Half-life (T1/2):	0.2

ADMET: Toxicity

hERG Blockers:	0.005
Human Hepatotoxicity (H-HT):	0.998
Drug-inuced Liver Injury (DILI):	0.987
AMES Toxicity:	0.003
Rat Oral Acute Toxicity:	0.496
Maximum Recommended Daily Dose:	0.95
Skin Sensitization:	0.011
Carcinogencity:	0.172
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.96

Download Data

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

Natural Product: NPC135558

Natural Product ID:	NPC135558
*Common Name:**	Bistratamide F
IUPAC Name:	n.a.
Synonyms:	Bistratamide F
Standard InCHIKey:	PVKWKGXPRJQDIZ-XZHCTYTHSA-N
Standard InCHI:	InChI=1S/C25H36N6O5S/c1-10(2)16-23-26-14(8-35-23)20(32)30-18(12(5)6)25-27-15(9-37-25)21(33)28-17(11(3)4)24-31-19(13(7)36-24)22(34)29-16/h9-14,16-19H,8H2,1-7H3,(H,28,33)(H,29,34)(H,30,32)/t13-,14+,16+,17+,18+,19+/m1/s1
SMILES:	CC(C)[C@H]1C2=N[C@@H](CO2)C(=N[C@@H](C(C)C)c2nc(cs2)C(=N[C@@H](C(C)C)C2=N[C@@H]([C@@H](C)O2)C(=N1)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL526699
PubChem CID:	11060498
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000348] Peptides [CHEMONTID:0001995] Cyclic peptides

*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
NPO22842	Lissoclinum bistratum	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12608858]
NPO22842	Lissoclinum bistratum	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7807120]
NPO22842	Lissoclinum bistratum	Species	Didemnidae	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	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	28.0	ug.mL-1	PMID[520683]

☑ 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 NPC135558 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	235
0.1-0.2	26944
0.2-0.3	12401
0.3-0.4	2880
0.4-0.5	118
0.5-0.6	78
0.6-0.7	22
0.7-0.8	10
0.8-0.85	0
0.85-0.9	1
0.9-0.95	4
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
0.9569	High Similarity	NPC267605
0.9402	High Similarity	NPC51692
0.9106	High Similarity	NPC74917
0.9091	High Similarity	NPC89592
0.9032	High Similarity	NPC120917
0.8814	High Similarity	NPC214375
0.7571	Intermediate Similarity	NPC475390
0.7432	Intermediate Similarity	NPC237219
0.7329	Intermediate Similarity	NPC50274
0.7305	Intermediate Similarity	NPC469801
0.7143	Intermediate Similarity	NPC103268
0.7044	Intermediate Similarity	NPC475330
0.7032	Intermediate Similarity	NPC24990
0.7	Intermediate Similarity	NPC263485
0.7	Intermediate Similarity	NPC25316
0.7	Intermediate Similarity	NPC229160
0.7	Intermediate Similarity	NPC174652
0.6928	Remote Similarity	NPC522
0.6928	Remote Similarity	NPC56058
0.6875	Remote Similarity	NPC161242
0.6875	Remote Similarity	NPC475534
0.6875	Remote Similarity	NPC476080
0.6815	Remote Similarity	NPC256912
0.6815	Remote Similarity	NPC34319
0.6795	Remote Similarity	NPC475554
0.6772	Remote Similarity	NPC164006
0.6731	Remote Similarity	NPC222391
0.671	Remote Similarity	NPC110129
0.671	Remote Similarity	NPC201014
0.6689	Remote Similarity	NPC319751
0.66	Remote Similarity	NPC473398
0.6564	Remote Similarity	NPC132662
0.6556	Remote Similarity	NPC119481
0.6516	Remote Similarity	NPC217981
0.646	Remote Similarity	NPC476103
0.6125	Remote Similarity	NPC216720
0.6087	Remote Similarity	NPC210424
0.6084	Remote Similarity	NPC134480
0.6048	Remote Similarity	NPC473704
0.6	Remote Similarity	NPC101980
0.6	Remote Similarity	NPC97078
0.6	Remote Similarity	NPC329961
0.6	Remote Similarity	NPC470146
0.6	Remote Similarity	NPC122427
0.5932	Remote Similarity	NPC165538
0.5845	Remote Similarity	NPC278902
0.5833	Remote Similarity	NPC475568
0.5804	Remote Similarity	NPC137705
0.5767	Remote Similarity	NPC315252
0.5714	Remote Similarity	NPC475604
0.5658	Remote Similarity	NPC474070
0.5617	Remote Similarity	NPC14101

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 NPC135558 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	98
0.1-0.2	2012
0.2-0.3	5126
0.3-0.4	1736
0.4-0.5	138
0.5-0.6	39
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
0.7176	Intermediate Similarity	NPD9579	Approved
0.5848	Remote Similarity	NPD2957	Phase 2
0.5839	Remote Similarity	NPD6915	Approved
0.5606	Remote Similarity	NPD879	Approved
0.5606	Remote Similarity	NPD878	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