NPASS Compound

Structure

NPC164006 OpenBabel07101718232D 43 45 0 0 1 0 0 0 0 0999 V2000 -4.2159 3.7933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8522 -1.2748 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0127 -0.1143 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3853 4.2838 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2234 -1.6360 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3516 -1.9325 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0807 -2.3038 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5458 3.1233 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9096 -0.8939 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9633 -0.8443 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3398 -1.7381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5024 3.1723 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1633 1.9783 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8398 1.5687 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0974 -0.3595 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6306 3.3685 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7379 2.2711 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4343 1.2404 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5332 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0307 3.1723 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9606 2.6985 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4274 0.3105 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4274 2.6985 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2711 2.2711 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7379 0.7379 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2711 0.7379 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5024 -0.1633 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0307 -0.1633 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2860 -1.7877 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2364 -2.7340 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -4.8021 -0.9930 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 3.0090 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.2949 1.5045 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.4343 1.7686 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.5332 3.0090 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.1790 4.1081 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0974 3.3685 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1154 0.3077 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3542 -1.0991 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9606 0.3105 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7582 2.0841 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.1633 1.0307 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 8 1 0 0 0 0 2 15 1 0 0 0 0 3 15 1 0 0 0 0 5 28 1 0 0 0 0 6 28 1 0 0 0 0 7 29 1 0 0 0 0 8 16 1 0 0 0 0 9 10 1 0 0 0 0 9 11 1 0 0 0 0 11 29 1 0 0 0 0 12 20 1 0 0 0 0 12 32 1 0 0 0 0 13 17 2 0 0 0 0 13 43 1 0 0 0 0 14 18 2 0 0 0 0 14 42 1 0 0 0 0 16 4 1 6 0 0 0 17 23 1 0 0 0 0 17 33 1 0 0 0 0 18 26 1 0 0 0 0 18 34 1 0 0 0 0 19 10 1 6 0 0 0 19 28 1 0 0 0 0 19 40 1 0 0 0 0 20 35 2 3 0 0 0 20 36 1 0 0 0 0 21 16 1 6 0 0 0 21 24 1 0 0 0 0 21 35 1 0 0 0 0 22 15 1 6 0 0 0 22 25 1 0 0 0 0 22 41 1 0 0 0 0 23 32 2 3 0 0 0 23 37 1 0 0 0 0 24 34 2 0 0 0 0 24 42 1 0 0 0 0 25 33 2 0 0 0 0 25 43 1 0 0 0 0 26 38 2 0 0 0 0 26 40 1 0 0 0 0 27 28 1 0 0 0 0 27 39 2 0 0 0 0 27 41 1 0 0 0 0 29 30 1 0 0 0 0 29 31 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	674.18
Volume:	627.548
LogP:	6.106
LogD:	4.705
LogS:	-4.841
# Rotatable Bonds:	7
TPSA:	136.58
# H-Bond Aceptor:	10
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	14

MedChem Properties

QED Drug-Likeness Score:	0.254
Synthetic Accessibility Score:	6.327
Fsp3:	0.655
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:	-4.73
MDCK Permeability:	2.208047590102069e-05
Pgp-inhibitor:	0.997
Pgp-substrate:	0.371
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.009
30% Bioavailability (F30%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.283
Plasma Protein Binding (PPB):	99.47476959228516%
Volume Distribution (VD):	0.526
Pgp-substrate:	1.8333879709243774%

ADMET: Metabolism

CYP1A2-inhibitor:	0.201
CYP1A2-substrate:	0.299
CYP2C19-inhibitor:	0.93
CYP2C19-substrate:	0.152
CYP2C9-inhibitor:	0.952
CYP2C9-substrate:	0.094
CYP2D6-inhibitor:	0.134
CYP2D6-substrate:	0.153
CYP3A4-inhibitor:	0.976
CYP3A4-substrate:	0.839

ADMET: Excretion

Clearance (CL):	3.202
Half-life (T1/2):	0.007

ADMET: Toxicity

hERG Blockers:	0.466
Human Hepatotoxicity (H-HT):	0.762
Drug-inuced Liver Injury (DILI):	0.932
AMES Toxicity:	0.005
Rat Oral Acute Toxicity:	0.07
Maximum Recommended Daily Dose:	0.724
Skin Sensitization:	0.035
Carcinogencity:	0.038
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.425

Download Data

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

Natural Product: NPC164006

Natural Product ID:	NPC164006
*Common Name:**	27-Deoxylyngbyabellin A
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	MXKVWNSSDRMDBC-PWZKMPOXSA-N
Standard InCHI:	InChI=1S/C29H40Cl2N4O6S2/c1-8-16(4)21-24-34-18(14-42-24)26(38)40-19(10-9-11-29(7,30)31)28(5,6)27(39)41-22(15(2)3)25-33-17(13-43-25)23(37)32-12-20(36)35-21/h13-16,19,21-22H,8-12H2,1-7H3,(H,32,37)(H,35,36)/t16-,19-,21-,22-/m0/s1
SMILES:	CC[C@H](C)[C@H]1c2nc(cs2)C(=O)O[C@@H](CCCC(C)(Cl)Cl)C(C)(C)C(=O)O[C@@H](C(C)C)c2nc(cs2)C(=NCC(=N1)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1223738
PubChem CID:	46939691
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0001961] Depsipeptides [CHEMONTID:0001994] Cyclic depsipeptides

*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
NPO30186	Lyngbya bouillonii	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18461997]
NPO30186	Lyngbya bouillonii	Species	Oscillatoriaceae	Bacteria	n.a.	Papua New Guinea	n.a.	PMID[20131814]
NPO30186	Lyngbya bouillonii	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[20704304]

☑ 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	2

Activity Type	# Activity
Cell Line	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	12.0	nM	PMID[487893]
NPT165	Cell Line	HeLa	Homo sapiens	IC50	=	7.3	nM	PMID[487893]

☑ 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 NPC164006 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	186
0.1-0.2	2357
0.2-0.3	25669
0.3-0.4	13129
0.4-0.5	1180
0.5-0.6	91
0.6-0.7	70
0.7-0.8	5
0.8-0.85	1
0.85-0.9	6
0.9-0.95	1
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9684	High Similarity	NPC132662
0.9057	High Similarity	NPC475554
0.8896	High Similarity	NPC134480
0.8841	High Similarity	NPC473704
0.8805	High Similarity	NPC216720
0.875	High Similarity	NPC210424
0.7436	Intermediate Similarity	NPC89592
0.7289	Intermediate Similarity	NPC475390
0.7241	Intermediate Similarity	NPC56058
0.7241	Intermediate Similarity	NPC522
0.7179	Intermediate Similarity	NPC51692
0.7169	Intermediate Similarity	NPC469801
0.7143	Intermediate Similarity	NPC74917
0.7099	Intermediate Similarity	NPC120917
0.7078	Intermediate Similarity	NPC214375
0.6989	Remote Similarity	NPC237219
0.6962	Remote Similarity	NPC267605
0.6897	Remote Similarity	NPC50274
0.6772	Remote Similarity	NPC135558
0.6726	Remote Similarity	NPC103268
0.6629	Remote Similarity	NPC119481
0.6571	Remote Similarity	NPC473398
0.6552	Remote Similarity	NPC319751
0.6519	Remote Similarity	NPC231110
0.6517	Remote Similarity	NPC154873
0.6484	Remote Similarity	NPC312887
0.648	Remote Similarity	NPC165538
0.648	Remote Similarity	NPC268063
0.648	Remote Similarity	NPC224609
0.6464	Remote Similarity	NPC474538
0.6462	Remote Similarity	NPC122427
0.6461	Remote Similarity	NPC185665
0.6461	Remote Similarity	NPC475737
0.6461	Remote Similarity	NPC474067
0.6461	Remote Similarity	NPC474094
0.6425	Remote Similarity	NPC61667
0.6425	Remote Similarity	NPC45576
0.6425	Remote Similarity	NPC109498
0.6425	Remote Similarity	NPC163147
0.6425	Remote Similarity	NPC32583
0.6425	Remote Similarity	NPC474090
0.6425	Remote Similarity	NPC252616
0.6413	Remote Similarity	NPC222391
0.64	Remote Similarity	NPC190329
0.6398	Remote Similarity	NPC256912
0.6398	Remote Similarity	NPC34319
0.6378	Remote Similarity	NPC329961
0.6374	Remote Similarity	NPC127775
0.6374	Remote Similarity	NPC52587
0.6364	Remote Similarity	NPC474069
0.6354	Remote Similarity	NPC202591
0.6354	Remote Similarity	NPC212214
0.6348	Remote Similarity	NPC82436
0.6348	Remote Similarity	NPC474103
0.6348	Remote Similarity	NPC474068
0.6348	Remote Similarity	NPC474064
0.6319	Remote Similarity	NPC21126
0.6313	Remote Similarity	NPC475683
0.6313	Remote Similarity	NPC474102
0.6313	Remote Similarity	NPC474079
0.6313	Remote Similarity	NPC157194
0.6313	Remote Similarity	NPC474080
0.6313	Remote Similarity	NPC21449
0.6304	Remote Similarity	NPC201014
0.6304	Remote Similarity	NPC110129
0.6283	Remote Similarity	NPC161242
0.6243	Remote Similarity	NPC474515
0.6243	Remote Similarity	NPC206724
0.6223	Remote Similarity	NPC97078
0.6223	Remote Similarity	NPC101980
0.6223	Remote Similarity	NPC470146
0.6218	Remote Similarity	NPC229160
0.6218	Remote Similarity	NPC25316
0.6218	Remote Similarity	NPC263485
0.6198	Remote Similarity	NPC476080
0.6198	Remote Similarity	NPC475534
0.6196	Remote Similarity	NPC315252
0.6166	Remote Similarity	NPC475330
0.6141	Remote Similarity	NPC217981
0.6138	Remote Similarity	NPC24990
0.6134	Remote Similarity	NPC174652
0.6127	Remote Similarity	NPC474070
0.6105	Remote Similarity	NPC476103
0.6095	Remote Similarity	NPC475350
0.6095	Remote Similarity	NPC14877
0.6095	Remote Similarity	NPC145178
0.6081	Remote Similarity	NPC469858
0.6009	Remote Similarity	NPC251036
0.5911	Remote Similarity	NPC475196
0.5854	Remote Similarity	NPC239660
0.5854	Remote Similarity	NPC106235
0.585	Remote Similarity	NPC96016
0.5726	Remote Similarity	NPC313966
0.5726	Remote Similarity	NPC314254
0.5714	Remote Similarity	NPC476829
0.5706	Remote Similarity	NPC145047
0.5706	Remote Similarity	NPC86490
0.5706	Remote Similarity	NPC137705
0.5632	Remote Similarity	NPC275393
0.5632	Remote Similarity	NPC475604

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 NPC164006 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	105
0.1-0.2	629
0.2-0.3	3692
0.3-0.4	4118
0.4-0.5	558
0.5-0.6	43
0.6-0.7	5
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
0.6486	Remote Similarity	NPD6916	Clinical (unspecified phase)
0.6461	Remote Similarity	NPD6907	Phase 2
0.6444	Remote Similarity	NPD6915	Approved
0.6319	Remote Similarity	NPD6910	Phase 3
0.623	Remote Similarity	NPD6911	Discontinued
0.6024	Remote Similarity	NPD9579	Approved
0.5854	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.5838	Remote Similarity	NPD2957	Phase 2
0.5637	Remote Similarity	NPD6632	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