NPASS Compound

Natural Product: NPC40959

Natural Product ID	NPC40959
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OZGKITZRRFNYRV-LTDGUKILSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5315428
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 3D 64 69 0 0 0 0 0 0 0 0999 V2000 -4.8079 -0.3933 1.7433 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1141 -0.3780 0.3725 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0232 0.2791 -0.5731 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7414 0.0836 0.5643 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0712 -1.0226 1.3455 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6340 -1.0283 1.3543 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0360 -1.9840 1.7745 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1334 0.1320 0.8531 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3739 0.9726 2.1361 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5392 0.9484 -0.1902 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3915 1.0624 -1.3670 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7019 1.6071 -0.8433 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4646 0.5619 -0.0340 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1861 1.2253 1.1254 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5488 0.0523 -0.9310 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7631 -0.4501 -0.2712 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9429 0.2256 -0.0403 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7905 -0.6466 0.5899 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1709 -1.7685 0.7304 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9379 -1.7116 0.2277 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0188 -0.8563 -1.8640 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3823 -1.9802 -1.3679 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6003 -3.1021 -1.8680 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4548 -1.7580 -0.2392 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4786 -0.4553 0.3726 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8904 -1.6023 1.0479 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0275 2.0048 -2.3041 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9511 0.5994 -0.5713 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6130 1.9287 -0.9840 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9918 -0.2384 -1.8102 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6021 -1.3710 -2.1193 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4672 -2.1440 -1.2284 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7203 -3.3345 -1.6148 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0636 -1.7709 -0.0066 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3793 0.3848 2.4103 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7075 -1.3609 2.2423 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8838 -0.1685 1.6535 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6974 0.1844 -1.6512 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4025 1.2735 -0.3172 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9666 -0.3583 -0.5788 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7950 0.9569 1.2919 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4945 -0.9705 2.3935 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4225 -2.0382 0.9943 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2341 0.6063 2.7067 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3420 2.0491 1.9234 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4932 0.8157 2.8522 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5485 2.0046 0.2265 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4710 0.0874 -1.8349 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2835 1.9974 -1.6826 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4369 2.4825 -0.1983 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1259 1.6646 0.7069 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6583 2.0904 1.5562 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4670 0.4696 1.8465 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8474 0.9671 -1.5645 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2127 1.2482 -0.2907 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8097 -0.4419 0.9194 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2538 -2.5773 0.2540 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4444 -2.1959 -0.4730 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3919 1.7762 -3.1713 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0747 1.9004 -1.9635 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2716 2.3185 -0.1583 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8374 2.7512 -1.0578 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3939 0.1547 -2.6547 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4370 -1.7592 -3.1398 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 1 8 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 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 15 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 25 26 1 1 11 27 1 0 10 28 1 0 28 29 1 6 28 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 32 34 1 0 34 2 1 0 28 4 1 0 25 8 1 0 25 13 1 0 20 16 2 0 26 24 1 0 1 35 1 0 1 36 1 0 1 37 1 0 3 38 1 0 3 39 1 0 3 40 1 0 4 41 1 0 5 42 1 0 5 43 1 0 9 44 1 0 9 45 1 0 9 46 1 0 10 47 1 0 11 48 1 6 12 49 1 0 12 50 1 0 14 51 1 0 14 52 1 0 14 53 1 0 15 54 1 0 17 55 1 0 18 56 1 0 20 57 1 0 24 58 1 1 27 59 1 0 29 60 1 0 29 61 1 0 29 62 1 0 30 63 1 0 31 64 1 0 M END

Standard InCHIKey	OZGKITZRRFNYRV-LTDGUKILSA-N
Standard InCHI	InChI=1S/C26H30O8/c1-22(2)15-10-16(28)25(5)18(23(15,3)8-6-17(29)33-22)14(27)11-24(4)19(13-7-9-31-12-13)32-21(30)20-26(24,25)34-20/h6-9,12,14-15,18-20,27H,10-11H2,1-5H3/t14-,15?,18?,19?,20+,23-,24?,25+,26+/m0/s1
SMILES	CC1(C)C2CC(=O)[C@]3(C)C([C@H](CC4(C)C(c5ccoc5)OC(=O)[C@@H]5[C@]34O5)O)[C@@]2(C)C=CC(=O)O1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	470.19	Volume:	461.416 ? Van der Waals volume.
Dense:	1.019	LogP:	1.525 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.59 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.539 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	32.0
TPSA:	115.57 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.492	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.79	Fsp³:	0.654
MCE-18:	191.442 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.474	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.083 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.073 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.064	Promiscuous compounds:	0.009

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.993	MDCK Permeability:	-4.796
Pgp-inhibitor:	0.167	Pgp-substrate:	0.304
PAMPA:	0.977 ? 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):	0.007
20% Bioavailability (F20%):	0.236	30% Bioavailability (F30%):	0.228
50% Bioavailability (F50%):	0.953

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.412	MRP1:	0.991
Plasma Protein Binding (PPB):	93.012%	Volume Distribution (VD):	-0.141
Fu:	7.701% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.933
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.012
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.026	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.279	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.03
CYP3A4-inhibitor:	0.976	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.215
HLM stability:	0.035 ? 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):

7.25

Half-life (T1/2):

1.669

ADMET: Toxicity

hERG Blockers:	0.065	hERG Blockers (10um):	0.364
Human Hepatotoxicity (H-HT):	0.251	Drug-induced Liver Injury (DILI):	0.807
AMES Toxicity:	0.27	Rat Oral Acute Toxicity:	0.853
Maximum Recommended Daily Dose:	0.979	Skin Sensitization:	0.733
Carcinogencity:	0.734	Eye Corrosion:	0.02
Eye Irritation:	0.926	Respiratory Toxicity:	0.903
Drug-induced Neurotoxicity:	0.066	Ototoxicity:	0.557
Hematotoxicity:	0.075	Drug-induced Nephrotoxicity:	0.561
Genotoxicity:	0.942	RPMI-8226 Immunitoxicity:	0.135
A549 Cytotoxicity:	0.004	Hek293 Cytotoxicity:	0.064
BCF:	0.611 ? 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:	3.366 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.342 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.734 ? 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
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11000023]
NPO26298	Zanthoxylum simulans	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26666037]
NPO26298	Zanthoxylum simulans	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7798955]
NPO26298	Zanthoxylum simulans	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26298	Zanthoxylum simulans	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26298	Zanthoxylum simulans	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26298	Zanthoxylum simulans	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26298	Zanthoxylum simulans	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19266	Clausena excavata	Species	Rutaceae	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

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

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 NPC40959 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	10062
0.1-0.2	38529
0.2-0.3	1113
0.3-0.4	103
0.4-0.5	26
0.5-0.6	18
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC23387
0.7662	Intermediate Similarity	NPC263265
0.6867	Remote Similarity	NPC476853
0.6627	Remote Similarity	NPC476861
0.6627	Remote Similarity	NPC476850
0.6506	Remote Similarity	NPC486207
0.6118	Remote Similarity	NPC476857
0.6047	Remote Similarity	NPC476860
0.5909	Remote Similarity	NPC476856
0.5862	Remote Similarity	NPC126723
0.5843	Remote Similarity	NPC476858
0.5795	Remote Similarity	NPC611267
0.5714	Remote Similarity	NPC60973
0.5714	Remote Similarity	NPC605384
0.5698	Remote Similarity	NPC51568
0.5698	Remote Similarity	NPC234660
0.5542	Remote Similarity	NPC476862
0.5506	Remote Similarity	NPC96443
0.5506	Remote Similarity	NPC237155
0.5506	Remote Similarity	NPC290400
0.5484	Remote Similarity	NPC123088
0.5476	Remote Similarity	NPC476863
0.5333	Remote Similarity	NPC305016
0.5294	Remote Similarity	NPC604270
0.5056	Remote Similarity	NPC470939
0.5054	Remote Similarity	NPC193798

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC40959 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3750
0.1-0.2	5376
0.2-0.3	24
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