NPASS Compound

Natural Product: NPC165218

Natural Product ID	NPC165218
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Moluccensin J
IUPAC Name	n.a.
Synonyms	Moluccensin J
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1087404
PubChem CID	46184329
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids [CHEMONTID:0002380] Limonoids

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 72 77 0 0 0 0 0 0 0 0999 V2000 6.9011 -0.6153 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7443 -2.1071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9579 -2.9888 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3740 -2.7172 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2172 -4.2090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7500 -3.8971 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 O 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 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 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 O 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 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5444 -2.4605 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9352 -3.0224 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8994 -1.8734 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1045 -0.6013 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 -2.2500 -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 -5.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -6.4952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5895 -6.2272 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4502 -7.2029 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3109 -8.1787 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5863 -9.6532 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1037 -7.6799 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2430 -8.6556 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3740 -5.7008 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6731 -6.4508 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0037 -6.3109 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0000 -5.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4266 -4.7326 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0579 0.8765 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3929 -0.7721 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4093 -0.4585 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7172 -4.2090 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1381 -2.4482 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 2.6491 -0.9642 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 -1.5025 -3.5396 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2981 -4.4779 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6664 0.7895 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7054 -1.6620 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7877 0.1013 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4328 -2.7879 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5230 -3.6951 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9673 -2.2864 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8547 -5.3935 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 -0.0000 -5.1962 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2920 -7.5741 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6939 -7.6610 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6919 -6.0818 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2839 -7.5568 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2278 -6.3336 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4259 -8.3422 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3823 -9.6314 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2187 -7.5164 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2672 -9.7949 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9721 -7.2008 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9231 -7.7498 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4231 -5.1517 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7537 -7.6099 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0396 -7.4600 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5573 -3.2383 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 5 6 1 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 15 21 1 0 21 22 1 6 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 6 26 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 28 34 1 0 34 35 1 6 34 36 1 0 36 37 1 0 37 38 1 6 34 5 1 0 37 6 1 0 25 9 1 0 37 26 1 0 21 10 1 0 20 16 2 0 1 39 1 0 1 40 1 0 1 41 1 0 5 42 1 6 6 43 1 6 11 44 1 0 11 45 1 0 15 46 1 1 17 47 1 0 18 48 1 0 20 49 1 0 22 50 1 0 22 51 1 0 22 52 1 0 23 53 1 0 23 54 1 0 24 55 1 0 24 56 1 0 25 57 1 6 27 58 1 0 27 59 1 0 27 60 1 0 28 61 1 1 29 62 1 0 29 63 1 0 33 64 1 0 33 65 1 0 33 66 1 0 35 67 1 0 35 68 1 0 35 69 1 0 36 70 1 0 36 71 1 0 38 72 1 0 M END

Standard InCHIKey	LSBZEHLCUALPOF-GBPDNJNKSA-N
Standard InCHI	InChI=1S/C29H34O9/c1-14(30)37-25-22-23(33)21-16(28(4)18(11-19(31)35-5)27(25,3)13-29(22,28)34)6-8-26(2)17(21)10-20(32)38-24(26)15-7-9-36-12-15/h7,9,12,16,18,22,24-25,34H,6,8,10-11,13H2,1-5H3/t16-,18-,22-,24-,25+,26+,27-,28+,29-/m0/s1
SMILES	CC(=O)O[C@@H]1[C@@H]2C(=O)C3=C4CC(=O)O[C@@H](c5ccoc5)[C@]4(C)CC[C@@H]3[C@]3(C)[C@@H](CC(=O)OC)[C@]1(C)C[C@]23O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	526.22	Volume:	519.458 ? Van der Waals volume.
Dense:	1.013	LogP:	1.678 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.873 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.167 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	31.0
TPSA:	129.34 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.463	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.08	Fsp³:	0.655
MCE-18:	148.75 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.129	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.036 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.005 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.029	Promiscuous compounds:	0.453

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.472	MDCK Permeability:	-4.866
Pgp-inhibitor:	0.298	Pgp-substrate:	0.061
PAMPA:	0.716 ? 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):	0.002
20% Bioavailability (F20%):	0.132	30% Bioavailability (F30%):	0.324
50% Bioavailability (F50%):	0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.996
Plasma Protein Binding (PPB):	63.45%	Volume Distribution (VD):	-0.177
Fu:	34.498% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.887
OATP1B3 inhibitor:	0.988	BCRP inhibitor:	0.151
BSEP inhibitor:	0.957

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.087
CYP2C19-inhibitor:	0.146	CYP2C19-substrate:	0.061
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.013
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.266
CYP3A4-inhibitor:	0.802	CYP3A4-substrate:	0.249
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.963
HLM stability:	0.978 ? 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):

6.891

Half-life (T1/2):

1.187

ADMET: Toxicity

hERG Blockers:	0.061	hERG Blockers (10um):	0.19
Human Hepatotoxicity (H-HT):	0.476	Drug-induced Liver Injury (DILI):	0.817
AMES Toxicity:	0.339	Rat Oral Acute Toxicity:	0.553
Maximum Recommended Daily Dose:	0.781	Skin Sensitization:	0.726
Carcinogencity:	0.787	Eye Corrosion:	0.001
Eye Irritation:	0.566	Respiratory Toxicity:	0.214
Drug-induced Neurotoxicity:	0.297	Ototoxicity:	0.475
Hematotoxicity:	0.251	Drug-induced Nephrotoxicity:	0.671
Genotoxicity:	0.951	RPMI-8226 Immunitoxicity:	0.104
A549 Cytotoxicity:	0.037	Hek293 Cytotoxicity:	0.093
BCF:	0.591 ? 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:	3.497 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.714 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.087 ? 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
NPO6445	Xylocarpus moluccensis	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20112995]
NPO6445	Xylocarpus moluccensis	Species	Meliaceae	Eukaryota	seeds	n.a.	n.a.	PMID[20146503]
NPO6445	Xylocarpus moluccensis	Species	Meliaceae	Eukaryota	seeds	Thai	n.a.	PMID[21733687]
NPO6445	Xylocarpus moluccensis	Species	Meliaceae	Eukaryota	seeds	n.a.	n.a.	PMID[22724531]
NPO6445	Xylocarpus moluccensis	Species	Meliaceae	Eukaryota	seeds	n.a.	n.a.	PMID[26114936]
NPO6445	Xylocarpus moluccensis	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6445	Xylocarpus moluccensis	Species	Meliaceae	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	5

Activity Type	# Activity
Cell line	3
Non-molecular	2

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
NPT845	Cell line	BT-474	Homo sapiens	IC50	>	10.0	ug.mL-1	PMID[14552779]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	10.0	ug.mL-1	PMID[26287401]
NPT323	Cell line	SW-620	Homo sapiens	IC50	>	10.0	ug.mL-1	PubChem BioAssay data set
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	10.0	ug.mL-1	PMID[20112995]

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 NPC165218 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	8376
0.1-0.2	39336
0.2-0.3	1901
0.3-0.4	196
0.4-0.5	32
0.5-0.6	11
0.6-0.7	4
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
0.7143	Intermediate Similarity	NPC478178
0.6977	Remote Similarity	NPC236004
0.6292	Remote Similarity	NPC478177
0.6235	Remote Similarity	NPC469503
0.6092	Remote Similarity	NPC292389
0.5957	Remote Similarity	NPC94763
0.5778	Remote Similarity	NPC469338
0.5652	Remote Similarity	NPC469849
0.5568	Remote Similarity	NPC178932
0.5543	Remote Similarity	NPC69028
0.5465	Remote Similarity	NPC142113
0.5208	Remote Similarity	NPC329180
0.5106	Remote Similarity	NPC606471
0.5104	Remote Similarity	NPC469576
0.5052	Remote Similarity	NPC276551
0.5052	Remote Similarity	NPC478179

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC165218 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3253
0.1-0.2	5838
0.2-0.3	59
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