NPASS Compound

Natural Product: NPC600388

Natural Product ID	NPC600388
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MMPSCNRRQGVBGG-ZDUSSCGKSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL114186
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 48 51 0 0 0 0 0 0 0 0999 V2000 5.2153 -2.0733 -0.0614 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2912 -1.0420 0.1128 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9592 -1.2594 -0.1971 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5329 -2.4635 -0.6698 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1957 -2.6139 -0.9588 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3134 -1.5970 -0.7900 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7559 -0.3501 -0.3072 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0752 -0.1855 -0.0017 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6523 0.9340 0.5210 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8280 0.8824 2.0029 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2113 0.6555 0.0650 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1753 1.9477 0.2038 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4246 2.4633 0.2148 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9330 3.0726 -1.0315 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8228 2.9301 0.3101 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5046 4.2787 0.4689 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1455 2.6137 0.2635 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5648 1.2942 0.1086 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5884 0.3426 0.0146 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9039 -1.1069 -0.0571 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1460 -1.7882 -1.1619 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2831 -1.3356 -0.0539 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.8332 -2.0175 1.0606 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1252 -0.3727 -0.6766 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0126 0.9769 0.0470 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1970 -1.7264 0.3300 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8534 -2.9627 0.4880 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3711 -2.3772 -1.1056 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2595 -3.2446 -0.7987 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8331 -3.5784 -1.3348 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3444 1.7910 2.3162 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8695 0.6879 2.4755 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4966 0.0198 2.1861 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0763 2.3081 -1.7926 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2971 3.9288 -1.3101 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9211 3.4710 -0.7361 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7005 4.8725 -0.3505 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9290 3.3487 0.3434 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4673 -1.5371 0.8972 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3288 -2.8769 -1.0675 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3627 -1.4264 -2.1647 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4652 -1.3095 1.6461 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4776 -2.8725 0.7715 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0189 -2.3415 1.7698 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1672 -0.7448 -0.6484 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8031 -0.2347 -1.7260 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4937 0.9050 1.0225 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5158 1.7133 -0.6380 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 7 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 12 15 1 0 15 16 1 0 15 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 20 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 8 3 1 0 19 11 1 0 21 6 1 0 25 18 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 5 30 1 0 10 31 1 0 10 32 1 0 10 33 1 0 14 34 1 0 14 35 1 0 14 36 1 0 16 37 1 0 17 38 1 0 20 39 1 1 21 40 1 0 21 41 1 0 23 42 1 0 23 43 1 0 23 44 1 0 24 45 1 0 24 46 1 0 25 47 1 0 25 48 1 0 M END

Standard InCHIKey	MMPSCNRRQGVBGG-ZDUSSCGKSA-N
Standard InCHI	InChI=1S/C20H23NO4/c1-21-8-7-12-10-14(22)19(24-3)18-16(12)13(21)9-11-5-6-15(23-2)20(25-4)17(11)18/h5-6,10,13,22H,7-9H2,1-4H3/t13-/m0/s1
SMILES	COc1ccc2c(c1OC)-c1c(OC)c(O)cc3c1[C@H](C2)N(C)CC3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	341.16	Volume:	350.589 ? Van der Waals volume.
Dense:	0.973	LogP:	2.057 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.183 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.638 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	20.0
TPSA:	51.16 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.929	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.122	Fsp³:	0.4
MCE-18:	75.571 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.546	Fluc inhibitor:	0.085 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.505 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.513 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.004	Promiscuous compounds:	0.719

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.914	MDCK Permeability:	-4.744
Pgp-inhibitor:	0.026	Pgp-substrate:	0.681
PAMPA:	0.031 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.028
20% Bioavailability (F20%):	0.787	30% Bioavailability (F30%):	0.856
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.396	MRP1:	0.968
Plasma Protein Binding (PPB):	63.565%	Volume Distribution (VD):	0.03
Fu:	37.086% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.859
OATP1B3 inhibitor:	0.978	BCRP inhibitor:	0.546
BSEP inhibitor:	0.497

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.02
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.898	CYP2C9-substrate:	0.026
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	0.084
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.465
CYP2B6-substrate:	0.996	CYP2C8-inhibitor:	0.133
HLM stability:	0.289 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

8.339

Half-life (T1/2):

2.227

ADMET: Toxicity

hERG Blockers:	0.42	hERG Blockers (10um):	0.695
Human Hepatotoxicity (H-HT):	0.514	Drug-induced Liver Injury (DILI):	0.038
AMES Toxicity:	0.675	Rat Oral Acute Toxicity:	0.718
Maximum Recommended Daily Dose:	0.904	Skin Sensitization:	0.608
Carcinogencity:	0.737	Eye Corrosion:	0.001
Eye Irritation:	0.147	Respiratory Toxicity:	0.955
Drug-induced Neurotoxicity:	0.846	Ototoxicity:	0.308
Hematotoxicity:	0.14	Drug-induced Nephrotoxicity:	0.356
Genotoxicity:	0.774	RPMI-8226 Immunitoxicity:	0.086
A549 Cytotoxicity:	0.258	Hek293 Cytotoxicity:	0.365
BCF:	1.64 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.077 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.728 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.762 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1016/S0031-9422(00)88469-1]
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1016/S0031-9422(00)88469-1]
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5852	Litsea glutinosa	Species	Lauraceae	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	Organism Name	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
Aggregation	4

Activity Type	# Activity
Organism	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Aggregation	=	78.6	%	PMID[10612588]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Aggregation	=	89.4	%	PMID[10612588]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Aggregation	=	86.5	%	PMID[10612588]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Aggregation	=	83.5	%	PMID[10612588]

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC600388 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	27059
0.1-0.2	20341
0.2-0.3	2168
0.3-0.4	198
0.4-0.5	64
0.5-0.6	16
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	0

Similarity Score	Similarity Level	Natural Product ID
0.7049	Intermediate Similarity	NPC117188
0.7049	Intermediate Similarity	NPC145832
0.6833	Remote Similarity	NPC13504
0.6774	Remote Similarity	NPC195075
0.6774	Remote Similarity	NPC253043
0.6774	Remote Similarity	NPC27410
0.6406	Remote Similarity	NPC247389
0.6406	Remote Similarity	NPC205421
0.6406	Remote Similarity	NPC607722
0.625	Remote Similarity	NPC136508
0.6094	Remote Similarity	NPC609009
0.6029	Remote Similarity	NPC320223
0.5909	Remote Similarity	NPC474931
0.5781	Remote Similarity	NPC158376
0.5634	Remote Similarity	NPC114364
0.5522	Remote Similarity	NPC605949
0.5493	Remote Similarity	NPC229166
0.5373	Remote Similarity	NPC212794
0.5303	Remote Similarity	NPC326316
0.5303	Remote Similarity	NPC81733
0.5278	Remote Similarity	NPC128560
0.5231	Remote Similarity	NPC99659
0.5231	Remote Similarity	NPC325871
0.5152	Remote Similarity	NPC135538
0.5152	Remote Similarity	NPC24233
0.5147	Remote Similarity	NPC606254
0.5139	Remote Similarity	NPC600118
0.507	Remote Similarity	NPC219341

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC600388 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4039
0.1-0.2	4911
0.2-0.3	184
0.3-0.4	12
0.4-0.5	4
0.5-0.6	0
0.6-0.7	0
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
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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