NPASS Compound

Structure

NPC473704 OpenBabel07101719502D 58 59 0 0 1 0 0 0 0 0999 V2000 15.6214 6.5260 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1600 2.4422 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7047 6.5260 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7047 4.8228 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7510 1.2862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 13.6547 3.1196 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4307 1.6818 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2524 -2.7992 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2975 -1.5563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 15.1297 7.3776 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0572 1.4642 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1376 -0.4478 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 14.1464 7.3776 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2404 0.5302 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9332 -1.0258 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.6880 3.1196 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2297 2.2680 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7308 -0.6580 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2415 0.9247 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1964 5.6744 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5466 0.7082 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 14.1464 3.9712 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3308 -1.5563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2415 1.9081 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7380 1.4164 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.4449 1.1082 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 12.6714 4.8228 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 13.6547 6.5260 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7047 3.1196 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 12.1797 5.6744 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7499 -0.0917 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.7547 1.4164 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8516 -0.4917 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4438 -0.2697 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8225 -2.4079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4460 2.4861 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8527 0.8862 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.8304 -2.0037 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8524 -1.9009 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 6.6259 -2.5817 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 7.1767 2.2119 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.6471 -1.4535 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 12.6714 6.5260 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 15.1297 3.9712 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2297 0.5648 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 14.1464 5.6744 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 10.2130 3.9712 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2393 -0.8477 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3308 -3.2595 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5488 3.4640 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8306 0.7835 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8058 -2.4079 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 10.2130 2.2680 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 13.6547 4.8228 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5477 2.0861 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5454 -0.6697 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1767 0.6209 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 1 10 1 0 0 0 0 2 11 1 0 0 0 0 3 20 1 0 0 0 0 4 20 1 0 0 0 0 6 22 1 0 0 0 0 8 38 1 0 0 0 0 9 52 1 0 0 0 0 10 13 1 0 0 0 0 11 37 1 0 0 0 0 12 14 1 0 0 0 0 12 15 1 0 0 0 0 13 28 1 0 0 0 0 15 38 1 0 0 0 0 16 29 1 0 0 0 0 17 25 1 0 0 0 0 17 53 1 0 0 0 0 18 23 2 0 0 0 0 18 58 1 0 0 0 0 19 24 2 0 0 0 0 19 57 1 0 0 0 0 21 5 1 6 0 0 0 21 26 1 0 0 0 0 21 34 1 0 0 0 0 22 44 2 0 0 0 0 22 54 1 0 0 0 0 23 35 1 0 0 0 0 23 42 1 0 0 0 0 24 36 1 0 0 0 0 24 41 1 0 0 0 0 25 32 1 0 0 0 0 25 45 1 1 0 0 0 26 14 1 1 0 0 0 26 55 1 0 0 0 0 27 16 1 1 0 0 0 27 30 1 0 0 0 0 27 54 1 0 0 0 0 28 43 2 3 0 0 0 28 46 1 0 0 0 0 29 47 2 0 0 0 0 29 53 1 0 0 0 0 30 20 1 6 0 0 0 30 43 1 0 0 0 0 31 33 1 0 0 0 0 31 37 1 0 0 0 0 31 56 1 1 0 0 0 32 41 2 0 0 0 0 32 57 1 0 0 0 0 33 42 2 0 0 0 0 33 58 1 0 0 0 0 34 48 2 0 0 0 0 34 56 1 0 0 0 0 35 49 2 0 0 0 0 35 52 1 0 0 0 0 36 50 2 0 0 0 0 36 55 1 0 0 0 0 37 7 1 6 0 0 0 37 51 1 0 0 0 0 38 39 1 0 0 0 0 38 40 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	895.26
Volume:	837.03
LogP:	5.084
LogD:	2.997
LogS:	-4.305
# Rotatable Bonds:	30
TPSA:	226.84
# H-Bond Aceptor:	16
# H-Bond Donor:	3
# Rings:	2
# Heavy Atoms:	20

MedChem Properties

QED Drug-Likeness Score:	0.061
Synthetic Accessibility Score:	5.516
Fsp3:	0.684
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:	-5.103
MDCK Permeability:	2.018948543991428e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.632
Human Intestinal Absorption (HIA):	0.479
20% Bioavailability (F20%):	0.62
30% Bioavailability (F30%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.169
Plasma Protein Binding (PPB):	98.38375091552734%
Volume Distribution (VD):	0.299
Pgp-substrate:	4.090167045593262%

ADMET: Metabolism

CYP1A2-inhibitor:	0.163
CYP1A2-substrate:	0.079
CYP2C19-inhibitor:	0.85
CYP2C19-substrate:	0.089
CYP2C9-inhibitor:	0.96
CYP2C9-substrate:	0.061
CYP2D6-inhibitor:	0.025
CYP2D6-substrate:	0.051
CYP3A4-inhibitor:	0.946
CYP3A4-substrate:	0.824

ADMET: Excretion

Clearance (CL):	4.429
Half-life (T1/2):	0.05

ADMET: Toxicity

hERG Blockers:	0.051
Human Hepatotoxicity (H-HT):	0.917
Drug-inuced Liver Injury (DILI):	0.948
AMES Toxicity:	0.004
Rat Oral Acute Toxicity:	0.015
Maximum Recommended Daily Dose:	0.019
Skin Sensitization:	0.021
Carcinogencity:	0.069
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.045

Download Data

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

Natural Product: NPC473704

Natural Product ID:	NPC473704
*Common Name:**	Lyngbyabellin D
IUPAC Name:	[(2R,3S)-7,7-dichloro-1-[(1R,2R)-2-hydroxy-1-(4-methoxycarbonyl-1,3-thiazol-2-yl)-2-methylbutoxy]-2-methyl-1-oxooctan-3-yl] 2-[(1R)-2-[(3S,4S)-3-acetyloxy-4-(butanoylamino)-5-methylhexanoyl]oxy-1-hydroxyethyl]-1,3-thiazole-4-carboxylate
Synonyms:	Lyngbyabellin D
Standard InCHIKey:	VDFRHOQVEAPBIB-KQFMKBBFSA-N
Standard InCHI:	InChI=1S/C38H55Cl2N3O13S2/c1-10-13-28(46)43-30(20(3)4)27(54-22(6)44)16-29(47)53-17-25(45)32-41-24(19-57-32)36(50)55-26(14-12-15-38(8,39)40)21(5)34(48)56-31(37(7,51)11-2)33-42-23(18-58-33)35(49)52-9/h18-21,25-27,30-31,45,51H,10-17H2,1-9H3,(H,43,46)/t21-,25-,26+,27+,30+,31+,37-/m1/s1
SMILES:	CCCC(=O)NC(C(C)C)C(CC(=O)OCC(C1=NC(=CS1)C(=O)OC(CCCC(C)(Cl)Cl)C(C)C(=O)OC(C2=NC(=CS2)C(=O)OC)C(C)(CC)O)O)OC(=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL449669
PubChem CID:	44566744
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0002995] Pentacarboxylic acids and derivatives

*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
NPO32881	Lyngbya sp.	Species	Oscillatoriaceae	Bacteria	n.a.	Palauan	n.a.	PMID[12141859]
NPO32881	Lyngbya sp.	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[12502348]
NPO32881	Lyngbya sp.	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[12762789]
NPO32881	Lyngbya sp.	Species	Oscillatoriaceae	Bacteria	n.a.	Palauan	n.a.	PMID[12762800]
NPO32881	Lyngbya sp.	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[14695793]
NPO32881	Lyngbya sp.	Species	Oscillatoriaceae	Bacteria	n.a.	Florida Everglades	n.a.	PMID[17432902]
NPO32881	Lyngbya sp.	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18693761]
NPO32881	Lyngbya sp.	Species	Oscillatoriaceae	Bacteria	n.a.	Florida Keys	n.a.	PMID[21705224]

☑ 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
NPT91	Cell Line	KB	Homo sapiens	IC50	=	100.0	nM	PMID[523549]

☑ 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 NPC473704 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	206
0.1-0.2	2438
0.2-0.3	23501
0.3-0.4	15121
0.4-0.5	1256
0.5-0.6	122
0.6-0.7	41
0.7-0.8	2
0.8-0.85	0
0.85-0.9	3
0.9-0.95	4
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9936	High Similarity	NPC134480
0.9423	High Similarity	NPC210424
0.9359	High Similarity	NPC216720
0.9146	High Similarity	NPC132662
0.8841	High Similarity	NPC164006
0.8773	High Similarity	NPC475554
0.7824	Intermediate Similarity	NPC56058
0.7824	Intermediate Similarity	NPC522
0.6667	Remote Similarity	NPC475390
0.6667	Remote Similarity	NPC89592
0.661	Remote Similarity	NPC119481
0.6559	Remote Similarity	NPC101980
0.6559	Remote Similarity	NPC470146
0.6559	Remote Similarity	NPC97078
0.6554	Remote Similarity	NPC473398
0.6552	Remote Similarity	NPC469801
0.6534	Remote Similarity	NPC319751
0.6514	Remote Similarity	NPC469858
0.6509	Remote Similarity	NPC74917
0.6471	Remote Similarity	NPC120917
0.6424	Remote Similarity	NPC51692
0.642	Remote Similarity	NPC214375
0.6378	Remote Similarity	NPC312887
0.6324	Remote Similarity	NPC237219
0.6324	Remote Similarity	NPC231110
0.6319	Remote Similarity	NPC50274
0.6292	Remote Similarity	NPC190329
0.627	Remote Similarity	NPC127775
0.627	Remote Similarity	NPC474538
0.6257	Remote Similarity	NPC474069
0.6243	Remote Similarity	NPC474103
0.6243	Remote Similarity	NPC82436
0.6243	Remote Similarity	NPC474068
0.6243	Remote Similarity	NPC474064
0.623	Remote Similarity	NPC474515
0.623	Remote Similarity	NPC206724
0.6228	Remote Similarity	NPC267605
0.6216	Remote Similarity	NPC21126
0.6209	Remote Similarity	NPC157194
0.6209	Remote Similarity	NPC474102
0.6209	Remote Similarity	NPC474080
0.6209	Remote Similarity	NPC21449
0.6209	Remote Similarity	NPC475683
0.6209	Remote Similarity	NPC474079
0.6175	Remote Similarity	NPC185665
0.6175	Remote Similarity	NPC474067
0.6175	Remote Similarity	NPC474094
0.6175	Remote Similarity	NPC475737
0.6162	Remote Similarity	NPC202591
0.6162	Remote Similarity	NPC212214
0.6141	Remote Similarity	NPC61667
0.6141	Remote Similarity	NPC252616
0.6141	Remote Similarity	NPC32583
0.6141	Remote Similarity	NPC45576
0.6141	Remote Similarity	NPC474090
0.6141	Remote Similarity	NPC154873
0.6141	Remote Similarity	NPC163147
0.6141	Remote Similarity	NPC109498
0.6136	Remote Similarity	NPC103268
0.6108	Remote Similarity	NPC268063
0.6108	Remote Similarity	NPC224609
0.6096	Remote Similarity	NPC52587
0.6059	Remote Similarity	NPC165538
0.6048	Remote Similarity	NPC135558
0.5961	Remote Similarity	NPC122427
0.5961	Remote Similarity	NPC329961
0.5959	Remote Similarity	NPC34319
0.5926	Remote Similarity	NPC315252
0.5859	Remote Similarity	NPC161242
0.5847	Remote Similarity	NPC313966
0.5847	Remote Similarity	NPC314254
0.5845	Remote Similarity	NPC106235
0.5845	Remote Similarity	NPC239660
0.5803	Remote Similarity	NPC222391
0.5795	Remote Similarity	NPC256912
0.5779	Remote Similarity	NPC475534
0.5779	Remote Similarity	NPC476080
0.5765	Remote Similarity	NPC476103
0.5764	Remote Similarity	NPC475196
0.5754	Remote Similarity	NPC474070
0.5721	Remote Similarity	NPC229160
0.5721	Remote Similarity	NPC25316
0.5721	Remote Similarity	NPC263485
0.5714	Remote Similarity	NPC145178
0.5714	Remote Similarity	NPC475350
0.5714	Remote Similarity	NPC14877
0.5699	Remote Similarity	NPC110129
0.5699	Remote Similarity	NPC201014
0.5672	Remote Similarity	NPC475330
0.5644	Remote Similarity	NPC174652
0.5636	Remote Similarity	NPC251036
0.5634	Remote Similarity	NPC476829

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 NPC473704 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	109
0.1-0.2	724
0.2-0.3	4027
0.3-0.4	3800
0.4-0.5	468
0.5-0.6	17
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
0.6519	Remote Similarity	NPD6915	Approved
0.6216	Remote Similarity	NPD6910	Phase 3
0.6211	Remote Similarity	NPD6916	Clinical (unspecified phase)
0.6205	Remote Similarity	NPD9579	Approved
0.6175	Remote Similarity	NPD6907	Phase 2
0.6129	Remote Similarity	NPD6911	Discontinued
0.5845	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.575	Remote Similarity	NPD2957	Phase 2
0.5723	Remote Similarity	NPD7916	Approved
0.5723	Remote Similarity	NPD7915	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