NPASS Compound

Natural Product: NPC143706

Natural Product ID	NPC143706
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Chaparrin
IUPAC Name	n.a.
Synonyms	Chaparrin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL470984
PubChem CID	441791
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0002119] Quassinoids

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 55 59 0 0 0 0 0 0 0 0999 V2000 1.8392 -3.5327 2.2702 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7358 -2.3607 1.8417 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2262 -1.3922 2.6861 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3844 -0.3906 2.1040 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9490 -0.9753 1.8125 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5668 -0.6521 0.5135 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0266 -0.7880 0.6201 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7162 -0.4908 -0.4777 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9719 -0.0683 -1.6540 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8402 0.8896 -1.3893 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1383 0.6783 -0.0888 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3393 0.5034 -0.2588 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0927 0.2525 1.0034 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3908 -0.4188 0.6302 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1204 -1.9102 0.4790 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1218 0.1816 -0.4997 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6972 -0.9700 -1.3406 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3865 1.0731 -1.4060 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0957 1.6512 -0.8074 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3585 2.4571 0.2723 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4839 1.6870 1.3991 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5145 2.3631 -1.8053 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9647 0.3844 -2.5669 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5098 1.8372 0.7991 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4614 2.1407 -1.4813 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4119 -1.2275 -2.2399 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7335 -1.2267 1.8562 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2395 0.3395 2.9589 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7024 -0.7349 2.6218 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8769 -2.1029 1.8781 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2242 -1.4251 -0.2378 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8004 -0.5526 -0.5248 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6769 0.3342 -2.4096 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1058 0.7424 -2.2322 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4906 -0.3709 -0.9257 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0405 -0.3449 1.5537 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0242 -2.4647 0.1843 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3327 -2.1220 -0.2431 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0431 0.7353 -0.1464 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1692 -0.4595 -2.2272 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9198 -1.6397 -1.7073 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5290 -1.4652 -0.8099 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9721 1.9616 -1.7361 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8813 2.0412 2.2572 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5443 1.7300 1.7317 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8223 2.1137 -2.7050 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6345 0.3888 -3.2695 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9557 2.7264 0.4480 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4509 1.6383 1.8617 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5945 2.0693 0.5822 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3518 2.4294 -2.4292 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4654 -1.1717 -3.2329 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7478 -1.6060 1.5421 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8888 -0.4195 2.5797 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2273 -2.0661 2.3654 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 2 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 14 15 1 0 14 16 1 0 16 17 1 0 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 19 22 1 6 18 23 1 0 11 24 1 1 10 25 1 0 9 26 1 0 7 27 1 0 15 2 1 0 13 4 1 0 11 6 1 0 19 12 1 0 13 21 1 1 4 28 1 1 5 29 1 0 5 30 1 0 6 31 1 6 8 32 1 0 9 33 1 6 10 34 1 6 12 35 1 6 14 36 1 1 15 37 1 0 15 38 1 0 16 39 1 1 17 40 1 0 17 41 1 0 17 42 1 0 18 43 1 6 21 44 1 0 21 45 1 0 22 46 1 0 23 47 1 0 24 48 1 0 24 49 1 0 24 50 1 0 25 51 1 0 26 52 1 0 27 53 1 0 27 54 1 0 27 55 1 0 M END

Standard InCHIKey	SYRCAVSNPCUQCQ-ZKNGBWAJSA-N
Standard InCHI	InChI=1S/C20H28O7/c1-8-4-12(21)16(24)18(3)10(8)5-13-19-7-26-20(25,17(18)19)15(23)9(2)11(19)6-14(22)27-13/h4,9-13,15-17,21,23-25H,5-7H2,1-3H3/t9-,10+,11+,12+,13-,15-,16-,17-,18-,19-,20+/m1/s1
SMILES	O=C1O[C@@H]2C[C@H]3C(=C[C@@H]([C@H]([C@@]3([C@@H]3[C@@]42[C@@H](C1)[C@@H](C)[C@H]([C@@]3(OC4)O)O)C)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	380.18	Volume:	367.953 ? Van der Waals volume.
Dense:	1.033	LogP:	0.278 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.138 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.392 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	24.0
TPSA:	116.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	5.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.344	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.563	Fsp³:	0.85
MCE-18:	127.73 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.47	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.025 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.118	Promiscuous compounds:	0.661

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.677	MDCK Permeability:	-4.833
Pgp-inhibitor:	0.0	Pgp-substrate:	0.849
PAMPA:	0.998 ? 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):	0.037
20% Bioavailability (F20%):	0.161	30% Bioavailability (F30%):	0.343
50% Bioavailability (F50%):	0.951

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.196
Plasma Protein Binding (PPB):	46.702%	Volume Distribution (VD):	-0.237
Fu:	54.931% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.969	BCRP inhibitor:	0.018
BSEP inhibitor:	0.2

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	0.988	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.218
HLM stability:	0.009 ? 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):

3.691

Half-life (T1/2):

2.931

ADMET: Toxicity

hERG Blockers:	0.014	hERG Blockers (10um):	0.502
Human Hepatotoxicity (H-HT):	0.375	Drug-induced Liver Injury (DILI):	0.526
AMES Toxicity:	0.524	Rat Oral Acute Toxicity:	0.819
Maximum Recommended Daily Dose:	0.962	Skin Sensitization:	0.997
Carcinogencity:	0.087	Eye Corrosion:	0.005
Eye Irritation:	0.758	Respiratory Toxicity:	0.996
Drug-induced Neurotoxicity:	0.132	Ototoxicity:	0.821
Hematotoxicity:	0.405	Drug-induced Nephrotoxicity:	0.906
Genotoxicity:	0.962	RPMI-8226 Immunitoxicity:	0.5
A549 Cytotoxicity:	0.014	Hek293 Cytotoxicity:	0.046
BCF:	0.448 ? 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:	3.24 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.081 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.001 ? 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
NPO22346	Simaba cedron	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9644063]
NPO22346	Simaba cedron	Species	Simaroubaceae	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	1
Organism	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
NPT168	Cell line	P388	Mus musculus	IC50	>	100.0	ug.mL-1	DrugMatrix in vitro pharmacology data
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.25	ug.mL-1	PMID[19459694]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.35	ug.mL-1	PMID[19459694]

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 NPC143706 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	17179
0.1-0.2	29993
0.2-0.3	2618
0.3-0.4	28
0.4-0.5	12
0.5-0.6	15
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	0

Similarity Score	Similarity Level	Natural Product ID
0.7541	Intermediate Similarity	NPC302146
0.7333	Intermediate Similarity	NPC201992
0.7213	Intermediate Similarity	NPC472534
0.6866	Remote Similarity	NPC469877
0.6765	Remote Similarity	NPC470628
0.6765	Remote Similarity	NPC608244
0.6571	Remote Similarity	NPC259306
0.6418	Remote Similarity	NPC485568
0.6324	Remote Similarity	NPC473968
0.5833	Remote Similarity	NPC470919
0.5781	Remote Similarity	NPC138372
0.5781	Remote Similarity	NPC106228
0.5753	Remote Similarity	NPC474046
0.5507	Remote Similarity	NPC11252
0.5507	Remote Similarity	NPC289312
0.5429	Remote Similarity	NPC485622
0.5429	Remote Similarity	NPC604056
0.5217	Remote Similarity	NPC51978
0.5217	Remote Similarity	NPC604470
0.5139	Remote Similarity	NPC485567
0.5068	Remote Similarity	NPC475775
0.5067	Remote Similarity	NPC485625
0.5067	Remote Similarity	NPC18547
0.5067	Remote Similarity	NPC474906

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC143706 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6309
0.1-0.2	2805
0.2-0.3	36
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