NPASS Compound

Structure

CID88943 OpenBabel06191715422D 29 33 0 0 1 0 0 0 0 0999 V2000 5.3907 3.7391 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5107 1.5283 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5107 2.5065 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2512 -0.9196 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1359 1.8602 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5043 -0.7488 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0385 1.0387 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0885 2.8087 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5041 0.9906 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.0886 1.2259 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1583 0.4532 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5508 -0.9542 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5509 1.1958 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6635 2.0174 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1360 0.1209 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.1583 1.5281 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4819 -0.4167 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3801 0.6585 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3801 -0.4167 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.4818 0.6583 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6545 0.5930 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3910 0.2956 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9498 -0.1217 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5507 -1.9442 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5510 2.1858 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7111 -0.6704 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1582 2.5064 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7216 -0.4167 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 14 1 0 0 0 0 3 14 1 0 0 0 0 4 19 1 0 0 0 0 5 9 1 0 0 0 0 6 15 1 0 0 0 0 7 21 1 0 0 0 0 8 1 1 6 0 0 0 8 14 1 0 0 0 0 8 27 1 0 0 0 0 9 15 1 6 0 0 0 9 20 1 0 0 0 0 10 14 1 0 0 0 0 10 16 1 0 0 0 0 10 22 2 0 0 0 0 11 15 1 1 0 0 0 11 16 1 0 0 0 0 11 23 1 0 0 0 0 12 17 1 0 0 0 0 12 19 1 0 0 0 0 12 24 2 0 0 0 0 13 18 1 0 0 0 0 13 20 1 0 0 0 0 13 25 2 0 0 0 0 15 26 1 1 0 0 0 16 5 1 1 0 0 0 16 27 1 0 0 0 0 17 6 1 6 0 0 0 17 20 1 0 0 0 0 17 28 1 0 0 0 0 18 7 1 6 0 0 0 18 19 1 0 0 0 0 18 29 1 0 0 0 0 28 29 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	444.1
Volume:	389.736
LogP:	1.335
LogD:	1.319
LogS:	-3.947
# Rotatable Bonds:	1
TPSA:	127.61
# H-Bond Aceptor:	9
# H-Bond Donor:	3
# Rings:	6
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.44
Synthetic Accessibility Score:	7.074
Fsp3:	0.833
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:	-5.636
MDCK Permeability:	1.384371080348501e-05
Pgp-inhibitor:	0.008
Pgp-substrate:	0.153
Human Intestinal Absorption (HIA):	0.237
20% Bioavailability (F20%):	0.956
30% Bioavailability (F30%):	0.946

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.072
Plasma Protein Binding (PPB):	57.25132369995117%
Volume Distribution (VD):	0.95
Pgp-substrate:	54.68207550048828%

ADMET: Metabolism

CYP1A2-inhibitor:	0.001
CYP1A2-substrate:	0.705
CYP2C19-inhibitor:	0.086
CYP2C19-substrate:	0.89
CYP2C9-inhibitor:	0.348
CYP2C9-substrate:	0.086
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.07
CYP3A4-inhibitor:	0.195
CYP3A4-substrate:	0.971

ADMET: Excretion

Clearance (CL):	5.274
Half-life (T1/2):	0.341

ADMET: Toxicity

hERG Blockers:	0.002
Human Hepatotoxicity (H-HT):	0.547
Drug-inuced Liver Injury (DILI):	0.972
AMES Toxicity:	0.239
Rat Oral Acute Toxicity:	0.179
Maximum Recommended Daily Dose:	0.035
Skin Sensitization:	0.892
Carcinogencity:	0.967
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.702

Download Data

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

Natural Product: NPC88943

Natural Product ID:	NPC88943
*Common Name:**	Deacetylsirodesmin Pl
IUPAC Name:	n.a.
Synonyms:	Deacetylsirodesmin PL
Standard InCHIKey:	ODGGLAWTFMFKDG-DKTCTLHISA-N
Standard InCHI:	InChI=1S/C18H24N2O7S2/c1-8-14(2,3)10(22)16(27-8)5-9-15(26,11(16)23)6-17-12(24)19(4)18(7-21,29-28-17)13(25)20(9)17/h8-9,11,21,23,26H,5-7H2,1-4H3/t8-,9-,11+,15+,16-,17-,18-/m1/s1
SMILES:	OC[C@@]12SS[C@@]3(N(C1=O)[C@@H]1C[C@@]4([C@H]([C@@]1(C3)O)O)O[C@@H](C(C4=O)(C)C)C)C(=O)N2C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL470102
PubChem CID:	15608380
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]
NPO4482	Leptosphaeria maculans	Species	Leptosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13627	Sphaeria macula	n.a.	n.a.	n.a.	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[539027]
NPT192	Organism	Brassica juncea	Brassica juncea	FC	=	8.0	n.a.	PMID[539027]

☑ 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 NPC88943 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	350
0.1-0.2	4137
0.2-0.3	18126
0.3-0.4	13855
0.4-0.5	5689
0.5-0.6	496
0.6-0.7	39
0.7-0.8	3
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	NPC956
0.7133	Intermediate Similarity	NPC25327
0.6763	Remote Similarity	NPC271115
0.6667	Remote Similarity	NPC8325
0.6619	Remote Similarity	NPC309731
0.6525	Remote Similarity	NPC202722
0.6525	Remote Similarity	NPC39041
0.6525	Remote Similarity	NPC241294
0.6525	Remote Similarity	NPC471845
0.6525	Remote Similarity	NPC471846
0.6456	Remote Similarity	NPC243412
0.6405	Remote Similarity	NPC474210
0.6364	Remote Similarity	NPC28542
0.6306	Remote Similarity	NPC469800
0.6301	Remote Similarity	NPC266910
0.6267	Remote Similarity	NPC212106
0.6258	Remote Similarity	NPC45813
0.6242	Remote Similarity	NPC474371
0.6216	Remote Similarity	NPC473477
0.6188	Remote Similarity	NPC276822
0.6115	Remote Similarity	NPC471844
0.6067	Remote Similarity	NPC211848
0.6053	Remote Similarity	NPC220396
0.6013	Remote Similarity	NPC309249
0.5957	Remote Similarity	NPC137453
0.5899	Remote Similarity	NPC227622
0.5882	Remote Similarity	NPC476951
0.5882	Remote Similarity	NPC160066
0.5879	Remote Similarity	NPC264958
0.5879	Remote Similarity	NPC15440
0.5879	Remote Similarity	NPC185590
0.5865	Remote Similarity	NPC476019
0.5844	Remote Similarity	NPC476497
0.5833	Remote Similarity	NPC322966
0.5806	Remote Similarity	NPC470539
0.58	Remote Similarity	NPC208118
0.58	Remote Similarity	NPC99905
0.58	Remote Similarity	NPC96080
0.5779	Remote Similarity	NPC476501
0.5779	Remote Similarity	NPC262880
0.5779	Remote Similarity	NPC247902
0.5762	Remote Similarity	NPC477238
0.5762	Remote Similarity	NPC238323
0.5759	Remote Similarity	NPC475987
0.5759	Remote Similarity	NPC313348
0.5759	Remote Similarity	NPC120420
0.5745	Remote Similarity	NPC97336
0.5723	Remote Similarity	NPC99864
0.5714	Remote Similarity	NPC309525
0.5705	Remote Similarity	NPC476967
0.5698	Remote Similarity	NPC316244
0.5647	Remote Similarity	NPC44200
0.5647	Remote Similarity	NPC12124
0.5639	Remote Similarity	NPC52533
0.5629	Remote Similarity	NPC477237

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 NPC88943 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	1981
0.2-0.3	4688
0.3-0.4	1823
0.4-0.5	406
0.5-0.6	95
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9545	High Similarity	NPD5193	Discontinued
0.6187	Remote Similarity	NPD8140	Approved
0.6187	Remote Similarity	NPD8307	Discontinued
0.5944	Remote Similarity	NPD8087	Discontinued
0.5906	Remote Similarity	NPD8345	Approved
0.5906	Remote Similarity	NPD8347	Approved
0.5906	Remote Similarity	NPD8346	Approved
0.5899	Remote Similarity	NPD8139	Approved
0.5899	Remote Similarity	NPD8086	Approved
0.5899	Remote Similarity	NPD8083	Approved
0.5899	Remote Similarity	NPD8138	Approved
0.5899	Remote Similarity	NPD8085	Approved
0.5899	Remote Similarity	NPD8084	Approved
0.5899	Remote Similarity	NPD8082	Approved
0.5857	Remote Similarity	NPD8276	Approved
0.5857	Remote Similarity	NPD8275	Approved
0.5816	Remote Similarity	NPD8081	Approved
0.5786	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.5775	Remote Similarity	NPD8393	Approved
0.5723	Remote Similarity	NPD8415	Approved
0.5658	Remote Similarity	NPD8274	Clinical (unspecified phase)

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