NPASS Compound

Structure

CID956 OpenBabel06191715322D 32 36 0 0 1 0 0 0 0 0999 V2000 5.4014 3.7464 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9618 -1.4955 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5236 1.5313 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5235 2.5115 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2514 -0.9200 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1421 1.8639 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5092 -0.7502 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0406 1.0407 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0985 2.8143 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8572 -1.0967 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5091 0.9925 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.0987 1.2284 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1666 0.4541 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5519 -0.9561 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5520 1.1982 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6747 2.0213 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1422 0.1212 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.1665 1.5312 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4848 -0.4175 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3809 0.6598 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3809 -0.4175 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.4847 0.6596 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6578 0.5942 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6502 -1.6728 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4016 0.2962 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5518 -1.9469 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5521 2.1890 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7184 -0.6717 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9595 -0.1220 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1664 2.5113 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7230 -0.4175 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 2 10 1 0 0 0 0 3 16 1 0 0 0 0 4 16 1 0 0 0 0 5 21 1 0 0 0 0 6 11 1 0 0 0 0 7 17 1 0 0 0 0 8 23 1 0 0 0 0 9 1 1 6 0 0 0 9 16 1 0 0 0 0 9 30 1 0 0 0 0 10 24 2 0 0 0 0 10 29 1 0 0 0 0 11 17 1 6 0 0 0 11 22 1 0 0 0 0 12 16 1 0 0 0 0 12 18 1 0 0 0 0 12 25 2 0 0 0 0 13 17 1 1 0 0 0 13 18 1 0 0 0 0 13 29 1 0 0 0 0 14 19 1 0 0 0 0 14 21 1 0 0 0 0 14 26 2 0 0 0 0 15 20 1 0 0 0 0 15 22 1 0 0 0 0 15 27 2 0 0 0 0 17 28 1 1 0 0 0 18 6 1 1 0 0 0 18 30 1 0 0 0 0 19 7 1 6 0 0 0 19 22 1 0 0 0 0 19 31 1 0 0 0 0 20 8 1 6 0 0 0 20 21 1 0 0 0 0 20 32 1 0 0 0 0 31 32 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	486.11
Volume:	430.481
LogP:	1.633
LogD:	1.607
LogS:	-4.155
# Rotatable Bonds:	3
TPSA:	133.68
# H-Bond Aceptor:	10
# H-Bond Donor:	2
# Rings:	6
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.394
Synthetic Accessibility Score:	6.982
Fsp3:	0.8
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:	-5.48
MDCK Permeability:	1.86736106115859e-05
Pgp-inhibitor:	0.147
Pgp-substrate:	0.023
Human Intestinal Absorption (HIA):	0.587
20% Bioavailability (F20%):	0.987
30% Bioavailability (F30%):	0.967

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.093
Plasma Protein Binding (PPB):	50.97269821166992%
Volume Distribution (VD):	1.181
Pgp-substrate:	52.52837371826172%

ADMET: Metabolism

CYP1A2-inhibitor:	0.002
CYP1A2-substrate:	0.592
CYP2C19-inhibitor:	0.164
CYP2C19-substrate:	0.886
CYP2C9-inhibitor:	0.571
CYP2C9-substrate:	0.063
CYP2D6-inhibitor:	0.004
CYP2D6-substrate:	0.056
CYP3A4-inhibitor:	0.464
CYP3A4-substrate:	0.973

ADMET: Excretion

Clearance (CL):	3.441
Half-life (T1/2):	0.186

ADMET: Toxicity

hERG Blockers:	0.001
Human Hepatotoxicity (H-HT):	0.511
Drug-inuced Liver Injury (DILI):	0.983
AMES Toxicity:	0.921
Rat Oral Acute Toxicity:	0.504
Maximum Recommended Daily Dose:	0.031
Skin Sensitization:	0.922
Carcinogencity:	0.97
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.17

Download Data

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

Natural Product: NPC956

Natural Product ID:	NPC956
*Common Name:**	Sirodesmin Pl
IUPAC Name:	n.a.
Synonyms:	Sirodesmin Pl
Standard InCHIKey:	KTAIGLOGMSQPCG-OQIMMBKLSA-N
Standard InCHI:	InChI=1S/C20H26N2O8S2/c1-9-16(3,4)12(25)18(30-9)6-11-17(28,13(18)29-10(2)24)7-19-14(26)21(5)20(8-23,32-31-19)15(27)22(11)19/h9,11,13,23,28H,6-8H2,1-5H3/t9-,11-,13+,17+,18-,19-,20-/m1/s1
SMILES:	C[C@@H]1C(C)(C)C(=O)[C@@]2(C[C@@H]3[C@@](C[C@@]45C(=O)N(C)[C@@](CO)(C(=O)N34)SS5)([C@@H]2OC(=O)C)O)O1
Synthetic Gene Cluster:	BGC0001044;
ChEMBL Identifier:	CHEMBL472531
PubChem CID:	15608374
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002389] Diazinanes [CHEMONTID:0000189] Piperazines [CHEMONTID:0001731] Dioxopiperazines [CHEMONTID:0003684] 2,5-dioxopiperazines [CHEMONTID:0001732] Thiodioxopiperazines [CHEMONTID:0001790] Epipolythiodioxopiperazines

*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
NPO4482	Leptosphaeria maculans	Species	Leptosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18701303]
NPO4482	Leptosphaeria maculans	Species	Leptosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22672981]
NPO10303	Cercophora areolata	Species	Lasiosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8792624]
NPO16724	Coelogyne ovalis	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2357	Acronychia baueri	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4482	Leptosphaeria maculans	Species	Leptosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14081	Derris eriocarpa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16724	Coelogyne ovalis	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2357	Acronychia baueri	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2357	Acronychia baueri	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16724	Coelogyne ovalis	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17465	Agropyron semicostatum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10303	Cercophora areolata	Species	Lasiosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6753	Othonna floribunda	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2357	Acronychia baueri	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17391	Betula fusca	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13627	Sphaeria macula	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO14081	Derris eriocarpa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4482	Leptosphaeria maculans	Species	Leptosphaeriaceae	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
Organism	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT193	Organism	Brassica napus	Brassica napus	FC	=	8.0	n.a.	PMID[473869]
NPT192	Organism	Brassica juncea	Brassica juncea	FC	=	8.0	n.a.	PMID[473869]

☑ 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 NPC956 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	358
0.1-0.2	4005
0.2-0.3	16930
0.3-0.4	13710
0.4-0.5	6832
0.5-0.6	801
0.6-0.7	59
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9695	High Similarity	NPC88943
0.7055	Intermediate Similarity	NPC25327
0.669	Remote Similarity	NPC241294
0.669	Remote Similarity	NPC202722
0.669	Remote Similarity	NPC471845
0.669	Remote Similarity	NPC471846
0.669	Remote Similarity	NPC39041
0.66	Remote Similarity	NPC8325
0.6573	Remote Similarity	NPC271115
0.651	Remote Similarity	NPC474371
0.6434	Remote Similarity	NPC309731
0.6424	Remote Similarity	NPC212106
0.6376	Remote Similarity	NPC473477
0.6296	Remote Similarity	NPC243412
0.6286	Remote Similarity	NPC471844
0.6275	Remote Similarity	NPC309249
0.6242	Remote Similarity	NPC474210
0.6241	Remote Similarity	NPC137453
0.619	Remote Similarity	NPC28542
0.6187	Remote Similarity	NPC227622
0.6176	Remote Similarity	NPC160066
0.6149	Remote Similarity	NPC469800
0.6133	Remote Similarity	NPC266910
0.6104	Remote Similarity	NPC476497
0.6101	Remote Similarity	NPC45813
0.6045	Remote Similarity	NPC476019
0.6039	Remote Similarity	NPC476501
0.6039	Remote Similarity	NPC476951
0.6037	Remote Similarity	NPC276822
0.6026	Remote Similarity	NPC477238
0.6015	Remote Similarity	NPC322966
0.6013	Remote Similarity	NPC120420
0.5975	Remote Similarity	NPC99864
0.5974	Remote Similarity	NPC309525
0.5962	Remote Similarity	NPC470539
0.593	Remote Similarity	NPC316244
0.5915	Remote Similarity	NPC97336
0.5909	Remote Similarity	NPC211848
0.5897	Remote Similarity	NPC220396
0.5894	Remote Similarity	NPC477237
0.5862	Remote Similarity	NPC67009
0.5821	Remote Similarity	NPC52533
0.5814	Remote Similarity	NPC475342
0.5778	Remote Similarity	NPC203170
0.5745	Remote Similarity	NPC220234
0.5741	Remote Similarity	NPC82129
0.574	Remote Similarity	NPC264958
0.574	Remote Similarity	NPC15440
0.574	Remote Similarity	NPC185590
0.5724	Remote Similarity	NPC476952
0.5714	Remote Similarity	NPC471843
0.5714	Remote Similarity	NPC277918
0.5698	Remote Similarity	NPC314050
0.5698	Remote Similarity	NPC315809
0.5687	Remote Similarity	NPC120335
0.5676	Remote Similarity	NPC182185
0.5667	Remote Similarity	NPC63191
0.5667	Remote Similarity	NPC471202
0.566	Remote Similarity	NPC476967
0.5655	Remote Similarity	NPC177518
0.5655	Remote Similarity	NPC154962
0.5655	Remote Similarity	NPC88890
0.5655	Remote Similarity	NPC114365
0.5655	Remote Similarity	NPC132304
0.5655	Remote Similarity	NPC123070
0.5655	Remote Similarity	NPC18044
0.5655	Remote Similarity	NPC323720
0.5655	Remote Similarity	NPC169089
0.5655	Remote Similarity	NPC18433
0.5649	Remote Similarity	NPC96080
0.5649	Remote Similarity	NPC88190
0.5649	Remote Similarity	NPC99905
0.5649	Remote Similarity	NPC208118
0.5646	Remote Similarity	NPC167044
0.5633	Remote Similarity	NPC470537
0.5633	Remote Similarity	NPC262880
0.5633	Remote Similarity	NPC280903
0.5633	Remote Similarity	NPC247902
0.5629	Remote Similarity	NPC470116
0.5629	Remote Similarity	NPC470115
0.5625	Remote Similarity	NPC313657
0.5617	Remote Similarity	NPC475987
0.5617	Remote Similarity	NPC313348
0.5616	Remote Similarity	NPC168890
0.5613	Remote Similarity	NPC238323
0.5608	Remote Similarity	NPC217041
0.56	Remote Similarity	NPC98870

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 NPC956 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	155
0.1-0.2	1984
0.2-0.3	4529
0.3-0.4	1898
0.4-0.5	468
0.5-0.6	105
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9848	High Similarity	NPD5193	Discontinued
0.6475	Remote Similarity	NPD8307	Discontinued
0.6475	Remote Similarity	NPD8140	Approved
0.6224	Remote Similarity	NPD8087	Discontinued
0.6187	Remote Similarity	NPD8082	Approved
0.6187	Remote Similarity	NPD8083	Approved
0.6187	Remote Similarity	NPD8085	Approved
0.6187	Remote Similarity	NPD8138	Approved
0.6187	Remote Similarity	NPD8086	Approved
0.6187	Remote Similarity	NPD8139	Approved
0.6187	Remote Similarity	NPD8084	Approved
0.6174	Remote Similarity	NPD8347	Approved
0.6174	Remote Similarity	NPD8345	Approved
0.6174	Remote Similarity	NPD8346	Approved
0.6143	Remote Similarity	NPD8275	Approved
0.6143	Remote Similarity	NPD8276	Approved
0.6099	Remote Similarity	NPD8081	Approved
0.6056	Remote Similarity	NPD8393	Approved
0.6038	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.5975	Remote Similarity	NPD8415	Approved
0.5921	Remote Similarity	NPD8274	Clinical (unspecified phase)
0.5845	Remote Similarity	NPD8300	Approved
0.5845	Remote Similarity	NPD8301	Approved
0.5822	Remote Similarity	NPD8305	Approved
0.5822	Remote Similarity	NPD8306	Approved
0.5779	Remote Similarity	NPD8080	Discontinued
0.5682	Remote Similarity	NPD882	Phase 2
0.5682	Remote Similarity	NPD883	Phase 2
0.5674	Remote Similarity	NPD3715	Approved
0.5674	Remote Similarity	NPD3713	Approved
0.5674	Remote Similarity	NPD3714	Approved
0.5663	Remote Similarity	NPD8384	Approved
0.5658	Remote Similarity	NPD8137	Clinical (unspecified phase)
0.5655	Remote Similarity	NPD4056	Clinical (unspecified phase)
0.5655	Remote Similarity	NPD4057	Clinical (unspecified phase)
0.5608	Remote Similarity	NPD6941	Approved
0.56	Remote Similarity	NPD8414	Discontinued

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