NPASS Compound

Natural Product: NPC131903

Natural Product ID	NPC131903
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Maoecrystal J
IUPAC Name	n.a.
Synonyms	Maoecrystal J
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1641879
PubChem CID	53317860
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 64 68 0 0 0 0 0 0 0 0999 V2000 -2.0421 5.0936 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8853 3.6018 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 -3.7500 1.2990 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 -1.5000 0.0000 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 -2.5981 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 2.6491 -1.6339 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 3.7981 -4.5264 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2077 -4.0134 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4681 -2.5362 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3567 -4.9776 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 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 2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5862 2.8518 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7841 3.4619 0.0000 O 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 2.6491 0.9642 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1595 -4.4101 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4200 -5.8874 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2709 -6.8515 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8296 -6.4004 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8285 5.9752 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4124 5.7037 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 -4.8991 0.3349 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 -3.2319 -1.1927 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 -2.3125 -1.0781 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 -3.5623 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7765 -2.1587 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 0.4895 -5.3743 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7981 -0.6697 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 3.2321 -3.0186 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9916 -4.9105 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5058 -5.9418 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3209 -3.8285 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5398 -6.2356 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 -1.3953 4.0944 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 3.0000 2.5981 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5230 -1.0971 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 4.0586 0.4512 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1660 -7.0814 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3165 -7.8099 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6684 -5.1569 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 6 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 1 11 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 15 17 1 0 11 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 23 1 1 23 24 2 0 20 25 1 1 20 26 1 0 26 27 1 0 19 28 1 0 10 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 23 2 1 0 22 3 1 0 21 6 1 0 27 7 1 0 18 7 1 0 1 33 1 0 1 34 1 0 3 35 1 6 4 36 1 0 4 37 1 0 5 38 1 0 5 39 1 0 6 40 1 1 8 41 1 0 8 42 1 0 9 43 1 0 9 44 1 0 10 45 1 6 12 46 1 0 12 47 1 0 12 48 1 0 13 49 1 0 13 50 1 0 17 51 1 0 17 52 1 0 17 53 1 0 18 54 1 1 19 55 1 6 22 56 1 0 22 57 1 0 25 58 1 0 27 59 1 0 27 60 1 0 28 61 1 0 32 62 1 0 32 63 1 0 32 64 1 0 M END

Standard InCHIKey	SLUROFCVEYCYDJ-MIWKWXCYSA-N
Standard InCHI	InChI=1S/C24H32O8/c1-12-15-5-6-16-22-8-7-17(32-14(3)26)21(4,10-30-13(2)25)18(22)20(28)24(29,31-11-22)23(16,9-15)19(12)27/h15-18,20,28-29H,1,5-11H2,2-4H3/t15-,16+,17+,18-,20+,21-,22-,23+,24+/m1/s1
SMILES	C=C1[C@@H]2CC[C@H]3[C@@]45CC[C@@H]([C@@](C)(COC(=O)C)[C@H]5[C@@H]([C@]([C@]3(C2)C1=O)(O)OC4)O)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	448.21	Volume:	440.654 ? Van der Waals volume.
Dense:	1.017	LogP:	1.246 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.692 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.342 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	26.0
TPSA:	119.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.493	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.83	Fsp³:	0.792
MCE-18:	133.116 ? 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:	0.494	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.147	Promiscuous compounds:	0.481

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.338	MDCK Permeability:	-4.776
Pgp-inhibitor:	0.581	Pgp-substrate:	0.903
PAMPA:	0.552 ? 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):	0.138
20% Bioavailability (F20%):	0.92	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.945
Plasma Protein Binding (PPB):	52.44%	Volume Distribution (VD):	-0.127
Fu:	52.547% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.025
BSEP inhibitor:	0.313

ADMET: Metabolism

CYP1A2-inhibitor:	0.327	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.005	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.051
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.021
CYP3A4-inhibitor:	0.056	CYP3A4-substrate:	0.094
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.308
HLM stability:	0.428 ? 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):

4.313

Half-life (T1/2):

1.413

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.14
Human Hepatotoxicity (H-HT):	0.516	Drug-induced Liver Injury (DILI):	0.616
AMES Toxicity:	0.922	Rat Oral Acute Toxicity:	0.529
Maximum Recommended Daily Dose:	0.396	Skin Sensitization:	0.996
Carcinogencity:	0.911	Eye Corrosion:	0.006
Eye Irritation:	0.565	Respiratory Toxicity:	0.273
Drug-induced Neurotoxicity:	0.131	Ototoxicity:	0.347
Hematotoxicity:	0.522	Drug-induced Nephrotoxicity:	0.443
Genotoxicity:	0.934	RPMI-8226 Immunitoxicity:	0.086
A549 Cytotoxicity:	0.14	Hek293 Cytotoxicity:	0.503
BCF:	0.604 ? 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:	3.609 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.606 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.912 ? 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]
NPO14739	Rabdosia 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[COCONUT]
NPO13742	Rabdosia macrophylla	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13742	Rabdosia macrophylla	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14739	Rabdosia eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13742	Rabdosia macrophylla	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14739	Rabdosia eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1927	Isodon eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14739	Rabdosia eriocalyx	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13742	Rabdosia macrophylla	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	=	4200.0	nM	PMID[20949916]
NPT181	Cell line	Bel-7402	Homo sapiens	IC50	>	10000.0	nM	PMID[20949916]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	=	9800.0	nM	PMID[20949916]

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 NPC131903 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	18870
0.1-0.2	25594
0.2-0.3	5129
0.3-0.4	188
0.4-0.5	51
0.5-0.6	11
0.6-0.7	8
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
0.7619	Intermediate Similarity	NPC320383
0.7302	Intermediate Similarity	NPC488136
0.7188	Intermediate Similarity	NPC56656
0.7121	Intermediate Similarity	NPC137104
0.7121	Intermediate Similarity	NPC325618
0.6923	Remote Similarity	NPC63841
0.6818	Remote Similarity	NPC320118
0.6418	Remote Similarity	NPC473410
0.6418	Remote Similarity	NPC471094
0.6418	Remote Similarity	NPC469984
0.6269	Remote Similarity	NPC85391
0.6154	Remote Similarity	NPC130511
0.6154	Remote Similarity	NPC307660
0.5821	Remote Similarity	NPC483201
0.5634	Remote Similarity	NPC488148
0.5571	Remote Similarity	NPC483206
0.5405	Remote Similarity	NPC274827
0.5352	Remote Similarity	NPC471474
0.5286	Remote Similarity	NPC205534
0.5205	Remote Similarity	NPC186054
0.5205	Remote Similarity	NPC483205
0.5205	Remote Similarity	NPC488140
0.5205	Remote Similarity	NPC474927
0.52	Remote Similarity	NPC474786

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC131903 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6312
0.1-0.2	2755
0.2-0.3	83
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