NPASS Compound

Natural Product: NPC469984

Natural Product ID	NPC469984
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Maoesin B
IUPAC Name	n.a.
Synonyms	Maoesin B
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1641893
PubChem CID	53317748
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003782] Kaurane diterpenoids

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

Chemical Representations

RDKit 2D 59 63 0 0 0 0 0 0 0 0999 V2000 6.3567 -0.2186 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2077 -1.1827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4681 -2.6600 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7981 -0.6697 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -1.6339 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -3.5623 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 0.9642 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 2.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2954 0.6125 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3828 -0.5621 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7372 3.5163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8940 5.0080 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4381 2.7663 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9322 3.3764 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 -3.5623 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5058 0.7456 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3209 -1.3676 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3926 0.9305 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2321 -2.1775 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1165 -0.5418 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7981 -4.5264 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8321 -4.8203 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2321 -3.0186 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0865 -4.5781 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4895 -5.3743 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 -5.3743 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 -4.4101 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9183 -2.1098 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2388 -1.1162 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9183 -0.4882 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0586 0.4512 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0000 2.5981 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7580 -0.8169 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 0.9642 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0861 -1.3808 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4095 -0.5130 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2863 -1.4724 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8991 2.2632 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8991 0.3349 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7500 3.8971 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2565 3.4369 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3953 4.0944 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6804 5.8897 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2643 5.6181 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0586 -3.0492 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 6 5 1 6 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 15 1 0 15 16 1 1 15 17 1 0 17 18 1 0 15 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 23 25 1 0 25 26 2 0 25 27 1 0 27 28 2 0 10 29 1 0 12 6 1 0 24 19 1 0 11 18 1 6 19 27 1 1 20 11 1 0 1 30 1 0 1 31 1 0 1 32 1 0 5 33 1 0 5 34 1 0 7 35 1 0 7 36 1 0 7 37 1 0 8 38 1 0 8 39 1 0 9 40 1 0 9 41 1 0 10 42 1 6 12 43 1 1 13 44 1 1 14 45 1 0 16 46 1 0 18 47 1 0 18 48 1 0 20 49 1 1 21 50 1 0 21 51 1 0 22 52 1 0 22 53 1 0 23 54 1 6 24 55 1 0 24 56 1 0 26 57 1 0 26 58 1 0 29 59 1 0 M END

Standard InCHIKey	UDOQTYDWKGQXFY-FTOXJWSDSA-N
Standard InCHI	InChI=1S/C22H30O7/c1-11-13-4-5-14-20-10-29-22(27,21(14,8-13)17(11)25)18(26)16(20)19(3,7-6-15(20)24)9-28-12(2)23/h13-16,18,24,26-27H,1,4-10H2,2-3H3/t13-,14+,15-,16-,18-,19+,20-,21+,22+/m1/s1
SMILES	CC(=O)OC[C@]1(C)CC[C@H]([C@@]23[C@@H]1[C@@H](O)[C@](O)(OC2)[C@]12[C@H]3CC[C@H](C1)C(=C)C2=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	406.2	Volume:	399.908 ? Van der Waals volume.
Dense:	1.016	LogP:	0.892 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.393 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.761 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	25.0
TPSA:	113.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.462	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.842	Fsp³:	0.818
MCE-18:	131.25 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.317	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.172	Promiscuous compounds:	0.522

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.298	MDCK Permeability:	-4.771
Pgp-inhibitor:	0.001	Pgp-substrate:	0.515
PAMPA:	0.969 ? 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):	0.034
20% Bioavailability (F20%):	0.81	30% Bioavailability (F30%):	0.958
50% Bioavailability (F50%):	0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007	MRP1:	0.587
Plasma Protein Binding (PPB):	54.084%	Volume Distribution (VD):	-0.088
Fu:	54.3% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.017
BSEP inhibitor:	0.569

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.037
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.621
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.023
CYP3A4-inhibitor:	0.083	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.824
HLM stability:	0.544 ? 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):

2.652

Half-life (T1/2):

2.588

ADMET: Toxicity

hERG Blockers:	0.034	hERG Blockers (10um):	0.122
Human Hepatotoxicity (H-HT):	0.536	Drug-induced Liver Injury (DILI):	0.262
AMES Toxicity:	0.81	Rat Oral Acute Toxicity:	0.764
Maximum Recommended Daily Dose:	0.866	Skin Sensitization:	0.996
Carcinogencity:	0.599	Eye Corrosion:	0.0
Eye Irritation:	0.276	Respiratory Toxicity:	0.879
Drug-induced Neurotoxicity:	0.028	Ototoxicity:	0.716
Hematotoxicity:	0.484	Drug-induced Nephrotoxicity:	0.59
Genotoxicity:	0.908	RPMI-8226 Immunitoxicity:	0.282
A549 Cytotoxicity:	0.133	Hek293 Cytotoxicity:	0.378
BCF:	0.511 ? 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:	3.334 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.061 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.161 ? 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
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	leaf	n.a.	PMID[17020288]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[20949916]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[20949916]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22624550]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	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
IC50	3

Activity Type	# Activity
Cell line	3

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
NPT139	Cell line	HT-29	Homo sapiens	IC50	>	10000.0	nM	DrugMatrix in vitro pharmacology data
NPT181	Cell line	Bel-7402	Homo sapiens	IC50	>	10000.0	nM	PMID[9514009]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	>	10000.0	nM	PubChem BioAssay data set

In vivo activity

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

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 NPC469984 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	20211
0.1-0.2	26361
0.2-0.3	3062
0.3-0.4	154
0.4-0.5	37
0.5-0.6	15
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	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC473410
1.0	High Similarity	NPC471094
0.7759	Intermediate Similarity	NPC130511
0.7759	Intermediate Similarity	NPC307660
0.7627	Intermediate Similarity	NPC483201
0.7541	Intermediate Similarity	NPC85391
0.7419	Intermediate Similarity	NPC56656
0.7258	Intermediate Similarity	NPC488136
0.6984	Remote Similarity	NPC488142
0.6984	Remote Similarity	NPC213320
0.697	Remote Similarity	NPC474786
0.6818	Remote Similarity	NPC137104
0.6818	Remote Similarity	NPC325618
0.6418	Remote Similarity	NPC488138
0.6418	Remote Similarity	NPC131903
0.6212	Remote Similarity	NPC471474
0.6061	Remote Similarity	NPC473397
0.6061	Remote Similarity	NPC488147
0.5882	Remote Similarity	NPC63841
0.5571	Remote Similarity	NPC483205
0.5571	Remote Similarity	NPC488140
0.5441	Remote Similarity	NPC205534
0.5352	Remote Similarity	NPC320383
0.5286	Remote Similarity	NPC102741
0.5286	Remote Similarity	NPC469725
0.5224	Remote Similarity	NPC55973
0.5224	Remote Similarity	NPC89860
0.5224	Remote Similarity	NPC189663
0.5224	Remote Similarity	NPC153234
0.5147	Remote Similarity	NPC488144
0.5147	Remote Similarity	NPC483202
0.5143	Remote Similarity	NPC488143
0.5072	Remote Similarity	NPC14634

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469984 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6610
0.1-0.2	2477
0.2-0.3	63
0.3-0.4	0
0.4-0.5	0
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