NPASS Compound

Structure

CID256912 OpenBabel06191716062D 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 0 0 0 0 0 0 0 0 0 0 -3.1493 -0.7794 0.0000 C 0 0 0 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 0 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 7 13 1 0 0 0 0 8 14 2 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 19 2 0 0 0 0 13 36 1 0 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 0 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:	528.22
Volume:	511.443
LogP:	5.16
LogD:	3.989
LogS:	-4.813
# Rotatable Bonds:	3
TPSA:	152.25
# H-Bond Aceptor:	11
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.459
Synthetic Accessibility Score:	6.037
Fsp3:	0.52
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:	-5.263
MDCK Permeability:	1.0587527867755853e-05
Pgp-inhibitor:	0.005
Pgp-substrate:	0.995
Human Intestinal Absorption (HIA):	0.007
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.704

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016
Plasma Protein Binding (PPB):	98.09628295898438%
Volume Distribution (VD):	4.544
Pgp-substrate:	2.293774127960205%

ADMET: Metabolism

CYP1A2-inhibitor:	0.163
CYP1A2-substrate:	0.145
CYP2C19-inhibitor:	0.61
CYP2C19-substrate:	0.061
CYP2C9-inhibitor:	0.857
CYP2C9-substrate:	0.021
CYP2D6-inhibitor:	0.019
CYP2D6-substrate:	0.149
CYP3A4-inhibitor:	0.784
CYP3A4-substrate:	0.236

ADMET: Excretion

Clearance (CL):	3.856
Half-life (T1/2):	0.058

ADMET: Toxicity

hERG Blockers:	0.016
Human Hepatotoxicity (H-HT):	0.929
Drug-inuced Liver Injury (DILI):	0.986
AMES Toxicity:	0.003
Rat Oral Acute Toxicity:	0.11
Maximum Recommended Daily Dose:	0.934
Skin Sensitization:	0.017
Carcinogencity:	0.255
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.94

Download Data

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

Natural Product: NPC256912

Natural Product ID:	NPC256912
*Common Name:**	Bistratamide G
IUPAC Name:	n.a.
Synonyms:	Bistratamide G
Standard InCHIKey:	YDONFAWPMVOOTI-BZSNNMDCSA-N
Standard InCHI:	InChI=1S/C25H32N6O5S/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/h8-12,16-18H,1-7H3,(H,28,33)(H,29,34)(H,30,32)/t16-,17-,18-/m0/s1
SMILES:	CC(C)[C@H]1c2nc(co2)C(=N[C@@H](C(C)C)c2nc(cs2)C(=N[C@@H](C(C)C)c2nc(c(C)o2)C(=N1)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL496043
PubChem CID:	10256384
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
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	=	5.0	ug.mL-1	PMID[558505]

☑ 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 NPC256912 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	394
0.1-0.2	17664
0.2-0.3	19938
0.3-0.4	4318
0.4-0.5	255
0.5-0.6	97
0.6-0.7	20
0.7-0.8	1
0.8-0.85	0
0.85-0.9	2
0.9-0.95	4
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
0.9673	High Similarity	NPC222391
0.9542	High Similarity	NPC201014
0.9542	High Similarity	NPC110129
0.9487	High Similarity	NPC34319
0.9346	High Similarity	NPC217981
0.9026	High Similarity	NPC50274
0.8861	High Similarity	NPC237219
0.7337	Intermediate Similarity	NPC235866
0.7115	Intermediate Similarity	NPC51692
0.6937	Remote Similarity	NPC89592
0.6903	Remote Similarity	NPC214375
0.6867	Remote Similarity	NPC103268
0.6824	Remote Similarity	NPC475390
0.6815	Remote Similarity	NPC135558
0.6768	Remote Similarity	NPC74917
0.6727	Remote Similarity	NPC120917
0.6717	Remote Similarity	NPC315872
0.6584	Remote Similarity	NPC267605
0.6398	Remote Similarity	NPC164006
0.623	Remote Similarity	NPC132662
0.6197	Remote Similarity	NPC49195
0.6064	Remote Similarity	NPC315411
0.6045	Remote Similarity	NPC469801
0.5895	Remote Similarity	NPC475554
0.5889	Remote Similarity	NPC315061
0.5882	Remote Similarity	NPC476830
0.5851	Remote Similarity	NPC216720
0.5837	Remote Similarity	NPC476831
0.5837	Remote Similarity	NPC476826
0.5837	Remote Similarity	NPC476827
0.5825	Remote Similarity	NPC134480
0.582	Remote Similarity	NPC210424
0.5811	Remote Similarity	NPC477219
0.5795	Remote Similarity	NPC473704
0.5785	Remote Similarity	NPC37924
0.5759	Remote Similarity	NPC476828
0.5759	Remote Similarity	NPC325683
0.5736	Remote Similarity	NPC476080
0.5736	Remote Similarity	NPC475534
0.5736	Remote Similarity	NPC161242
0.5727	Remote Similarity	NPC477218
0.5707	Remote Similarity	NPC475330
0.5683	Remote Similarity	NPC299035
0.5683	Remote Similarity	NPC177432
0.5678	Remote Similarity	NPC263485
0.5678	Remote Similarity	NPC25316
0.5678	Remote Similarity	NPC229160
0.5678	Remote Similarity	NPC174652
0.5667	Remote Similarity	NPC476829
0.5658	Remote Similarity	NPC322800
0.5658	Remote Similarity	NPC168135
0.5654	Remote Similarity	NPC56058
0.5654	Remote Similarity	NPC522
0.5644	Remote Similarity	NPC96016
0.5619	Remote Similarity	NPC295653
0.5619	Remote Similarity	NPC107458
0.561	Remote Similarity	NPC329961
0.561	Remote Similarity	NPC122427

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 NPC256912 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	161
0.1-0.2	1712
0.2-0.3	4171
0.3-0.4	2794
0.4-0.5	276
0.5-0.6	35
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
0.6717	Remote Similarity	NPD6444	Clinical (unspecified phase)
0.6127	Remote Similarity	NPD7896	Approved
0.5885	Remote Similarity	NPD2623	Phase 1

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