NPASS Compound

Natural Product: NPC479450

Natural Product ID	NPC479450
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LIZDXZFBFUVURO-KTZFTNIGSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
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 70 72 0 0 0 0 0 0 0 0999 V2000 7.9333 1.8199 -0.0889 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9906 0.4536 0.5908 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8453 0.3235 1.4997 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9660 0.6467 2.6994 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5719 -0.1745 1.0293 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4826 -0.3341 1.8607 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2967 -0.8017 1.3561 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1473 -1.1290 0.0057 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2363 -0.9693 -0.8237 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4163 -0.4972 -0.2898 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1942 -1.2639 -2.1721 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3384 -1.0811 -2.9695 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9395 -1.6017 -0.4880 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9103 -0.8029 -0.9553 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4094 -1.0910 -2.3361 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2151 0.2411 -2.7828 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3205 0.5374 -1.8276 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0849 0.1917 -0.4067 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4508 -0.2139 0.1719 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3750 0.7950 -0.0620 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6324 0.4876 0.4257 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1314 1.4483 1.4689 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.6186 1.6234 1.2857 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.2902 0.2922 1.0762 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.6363 -0.3746 -0.1061 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.2039 -1.7783 0.2814 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5780 0.3845 -0.5979 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6238 0.5634 0.7106 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2114 2.2218 2.4001 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9464 0.8827 2.7442 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2317 -0.8398 -0.1370 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5528 1.9323 -1.8790 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7091 0.1494 -4.0739 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3286 -1.5510 -3.2323 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1963 -0.9622 2.1990 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3397 -0.6352 3.5536 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5564 1.7040 -1.1460 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2433 2.4874 0.4495 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9424 2.2683 -0.1901 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0739 -0.3084 -0.1859 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9636 0.4817 1.1811 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6182 -0.0729 2.9137 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2449 -0.3811 -0.9646 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1997 -1.4647 -3.9989 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2040 -1.6673 -2.5499 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6663 -0.0381 -3.0310 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2610 0.2686 -0.8792 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4798 -1.7888 -2.2795 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5959 0.9921 -2.6736 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2361 0.0261 -2.2115 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7846 1.0847 0.2002 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8090 -1.1005 -0.3984 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2873 -0.4292 1.2461 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5639 -0.5191 0.8870 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5948 2.4103 1.4643 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8450 2.2499 0.3985 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3046 -0.3431 1.9826 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3453 -0.4853 -0.9779 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3268 -2.0482 -0.3276 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0223 -2.5025 0.0725 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0193 -1.8634 1.3828 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5924 1.0967 -0.1386 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8894 3.1488 2.5283 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3848 0.0008 2.7637 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4707 2.3573 -0.9901 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0331 -0.3460 -4.6386 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5017 -2.5089 -3.0252 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7002 0.4217 3.7092 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0916 -1.3202 4.0280 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3959 -0.7039 4.1222 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 3 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 8 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 25 27 1 0 24 28 1 0 23 29 1 0 22 30 1 0 18 31 1 0 17 32 1 0 16 33 1 0 15 34 1 0 7 35 1 0 35 36 1 0 10 5 1 0 31 14 1 0 27 21 1 0 1 37 1 0 1 38 1 0 1 39 1 0 2 40 1 0 2 41 1 0 6 42 1 0 10 43 1 0 12 44 1 0 12 45 1 0 12 46 1 0 14 47 1 6 15 48 1 1 16 49 1 6 17 50 1 6 18 51 1 1 19 52 1 0 19 53 1 0 21 54 1 1 22 55 1 1 23 56 1 6 24 57 1 1 25 58 1 6 26 59 1 0 26 60 1 0 26 61 1 0 28 62 1 0 29 63 1 0 30 64 1 0 32 65 1 0 33 66 1 0 34 67 1 0 36 68 1 0 36 69 1 0 36 70 1 0 M END

Standard InCHIKey	LIZDXZFBFUVURO-KTZFTNIGSA-N
Standard InCHI	InChI=1S/C23H34O13/c1-5-11(24)10-6-12(31-3)21(13(7-10)32-4)36-23-20(30)18(28)16(26)14(35-23)8-33-22-19(29)17(27)15(25)9(2)34-22/h6-7,9,14-20,22-23,25-30H,5,8H2,1-4H3/t9-,14+,15-,16+,17+,18-,19+,20+,22+,23-/m0/s1
SMILES	CCC(=O)c1cc(c(c(c1)OC)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO[C@H]2[C@@H]([C@@H]([C@H]([C@H](C)O2)O)O)O)O1)O)O)O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	518.2	Volume:	484.422 ? Van der Waals volume.
Dense:	1.07	LogP:	-0.588 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.195 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.121 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	19.0
TPSA:	193.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	6.0	Rings:	3.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.203	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.41	Fsp³:	0.696
MCE-18:	84.308 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.401	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.116 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.061 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.163	Promiscuous compounds:	0.061

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.706	MDCK Permeability:	-4.995
Pgp-inhibitor:	0.002	Pgp-substrate:	0.953
PAMPA:	0.976 ? 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):	0.121
20% Bioavailability (F20%):	0.029	30% Bioavailability (F30%):	0.214
50% Bioavailability (F50%):	0.795

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.094	MRP1:	0.411
Plasma Protein Binding (PPB):	63.488%	Volume Distribution (VD):	-0.437
Fu:	37.096% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.896
OATP1B3 inhibitor:	0.968	BCRP inhibitor:	0.054
BSEP inhibitor:	0.157

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.021
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.671
HLM stability:	0.19 ? 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):

1.517

Half-life (T1/2):

3.208

ADMET: Toxicity

hERG Blockers:	0.038	hERG Blockers (10um):	0.237
Human Hepatotoxicity (H-HT):	0.232	Drug-induced Liver Injury (DILI):	0.454
AMES Toxicity:	0.788	Rat Oral Acute Toxicity:	0.012
Maximum Recommended Daily Dose:	0.012	Skin Sensitization:	0.619
Carcinogencity:	0.041	Eye Corrosion:	0.0
Eye Irritation:	0.014	Respiratory Toxicity:	0.012
Drug-induced Neurotoxicity:	0.01	Ototoxicity:	0.962
Hematotoxicity:	0.33	Drug-induced Nephrotoxicity:	0.659
Genotoxicity:	0.113	RPMI-8226 Immunitoxicity:	0.239
A549 Cytotoxicity:	0.194	Hek293 Cytotoxicity:	0.224
BCF:	0.189 ? 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:	2.933 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.351 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.586 ? 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
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	n.a.	aerial part	n.a.	PMID[18991207]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	essential oil	Tibet	n.a.	PMID[20944522]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	Twigs	n.a.	n.a.	PMID[28541690]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36552598]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37746728]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39013008]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39395223]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29110	Litsea cubeba	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29110	Litsea cubeba	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
Activity	1

Activity Type	# Activity
Cell line	1

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
NPT65	Cell line	HepG2	Homo sapiens	Activity	=	37.6	%	PMID[28541690]

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 NPC479450 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	10217
0.1-0.2	34322
0.2-0.3	4413
0.3-0.4	748
0.4-0.5	138
0.5-0.6	17
0.6-0.7	2
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
0.6061	Remote Similarity	NPC480467
0.6029	Remote Similarity	NPC469622
0.5714	Remote Similarity	NPC293629
0.5658	Remote Similarity	NPC114740
0.5526	Remote Similarity	NPC3293
0.5479	Remote Similarity	NPC213723
0.5412	Remote Similarity	NPC44328
0.5412	Remote Similarity	NPC79056
0.5366	Remote Similarity	NPC99957
0.5362	Remote Similarity	NPC79908
0.5342	Remote Similarity	NPC469621
0.5238	Remote Similarity	NPC271270
0.5195	Remote Similarity	NPC471028
0.5172	Remote Similarity	NPC475155
0.5128	Remote Similarity	NPC40664
0.5128	Remote Similarity	NPC197723
0.5116	Remote Similarity	NPC43587
0.5116	Remote Similarity	NPC241016
0.5065	Remote Similarity	NPC23253

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479450 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3240
0.1-0.2	5742
0.2-0.3	155
0.3-0.4	7
0.4-0.5	5
0.5-0.6	1
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
0.5412	Remote Similarity	NPD7074	Phase 3

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