NPASS Compound

Natural Product: NPC469503

Natural Product ID	NPC469503
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	USQWQRAKBGJPTC-ANKFCNIWSA-N
IUPAC Name	n.a.
Synonyms	2-Hydroxy Fissinolid
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1081404
PubChem CID	46878891
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 75 79 0 0 0 0 0 0 0 0999 V2000 -2.7109 5.1728 -0.9476 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0742 3.8382 -0.7897 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6759 3.0080 0.2539 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9266 3.5750 1.0839 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1013 1.6372 0.3436 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1505 0.5035 0.2158 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0182 -0.7659 0.3708 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2419 -0.7269 -0.4970 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5798 -0.7067 1.8091 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2320 -2.0338 0.2815 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0765 -3.1349 0.2041 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2483 -4.1653 1.0708 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5199 -4.1013 2.0899 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1782 -5.3005 0.9189 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1050 -2.0128 -0.7039 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2249 -0.8710 -1.6423 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1960 0.4807 -0.8892 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4526 1.4909 -1.9967 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2685 0.6127 -0.5425 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6164 1.7176 0.3678 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0319 1.7543 0.8054 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9304 0.6761 0.2502 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1866 -0.6047 0.2805 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9006 -0.6522 -0.0994 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2403 -1.9726 -0.0444 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8172 -1.8883 0.7196 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9908 -1.6838 1.5603 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6927 -2.7052 1.8426 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2538 -0.4088 1.9864 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1627 0.6680 1.1128 C 0 0 1 0 0 0 0 0 0 0 0 0 5.4338 0.7139 0.3293 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2155 1.8321 0.0427 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2917 1.4165 -0.7028 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1751 0.1256 -0.8616 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0978 -0.3360 -0.2729 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2917 0.9607 -1.2029 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0730 -0.8414 -2.4727 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4392 5.7947 -0.3492 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7165 5.3666 -0.4908 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6957 5.4905 -2.0111 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9579 1.4609 -0.3799 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6474 1.5409 1.3381 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5627 0.4526 1.1613 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0873 -0.2120 -1.4601 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0918 -0.1875 -0.0040 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6414 -1.7238 -0.7473 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9526 -0.0495 2.4397 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6546 -1.6743 2.2884 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5974 -0.2472 1.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7368 -2.1464 1.2737 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6786 -5.5835 1.8745 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6247 -6.1556 0.4777 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9890 -5.0470 0.1938 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0784 -2.9428 -1.3466 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0415 -0.9186 -2.3716 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4915 1.5965 -2.2876 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9269 2.4650 -1.7735 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9087 1.1330 -2.9067 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7511 0.8594 -1.5516 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0055 1.6677 1.2842 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3953 2.7308 -0.0813 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5475 2.7276 0.5556 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1388 1.7049 1.9302 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0494 -2.1639 1.0549 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9215 -2.7975 -0.3372 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0971 -2.5317 -0.1368 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0480 -2.4106 1.3615 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2221 1.5848 1.7761 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9993 2.8388 0.3580 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0954 2.0336 -1.0935 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8076 -1.3573 -0.2748 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8779 1.9525 -1.5402 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3841 1.0479 -1.3679 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9869 0.1222 -1.8860 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3921 -1.6931 -2.4712 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 1 0 6 7 1 0 7 8 1 0 7 9 1 0 7 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 10 15 1 0 15 16 1 0 16 17 1 0 17 18 1 6 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 23 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 1 0 22 36 1 6 16 37 1 0 17 6 1 0 24 19 1 0 35 31 2 0 25 15 1 0 30 22 1 0 1 38 1 0 1 39 1 0 1 40 1 0 5 41 1 0 5 42 1 0 6 43 1 1 8 44 1 0 8 45 1 0 8 46 1 0 9 47 1 0 9 48 1 0 9 49 1 0 10 50 1 1 14 51 1 0 14 52 1 0 14 53 1 0 15 54 1 6 16 55 1 0 18 56 1 0 18 57 1 0 18 58 1 0 19 59 1 6 20 60 1 0 20 61 1 0 21 62 1 0 21 63 1 0 25 64 1 0 25 65 1 0 26 66 1 0 26 67 1 0 30 68 1 1 32 69 1 0 33 70 1 0 35 71 1 0 36 72 1 0 36 73 1 0 36 74 1 0 37 75 1 0 M END

Standard InCHIKey	USQWQRAKBGJPTC-ANKFCNIWSA-N
Standard InCHI	InChI=1S/C29H38O8/c1-15(30)36-26-18-11-17-19(29(5,24(18)33)21(27(26,2)3)13-22(31)34-6)7-9-28(4)20(17)12-23(32)37-25(28)16-8-10-35-14-16/h8,10,14,18-19,21,24-26,33H,7,9,11-13H2,1-6H3/t18-,19+,21+,24?,25+,26+,28-,29-/m1/s1
SMILES	COC(=O)C[C@H]1C(C)(C)[C@@H](OC(=O)C)[C@H]2C([C@]1(C)[C@H]1CC[C@@]3(C(=C1C2)CC(=O)O[C@H]3c1ccoc1)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	514.26	Volume:	521.861 ? Van der Waals volume.
Dense:	0.985	LogP:	2.21 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.521 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.591 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	28.0
TPSA:	112.27 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.355	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.877	Fsp³:	0.69
MCE-18:	127.102 ? 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:	0.481	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.089 ? 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:	0.014	Promiscuous compounds:	0.052

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.341	MDCK Permeability:	-5.02
Pgp-inhibitor:	0.819	Pgp-substrate:	0.074
PAMPA:	0.36 ? 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):	0.006
20% Bioavailability (F20%):	0.168	30% Bioavailability (F30%):	0.708
50% Bioavailability (F50%):	0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.02	MRP1:	0.978
Plasma Protein Binding (PPB):	62.857%	Volume Distribution (VD):	-0.328
Fu:	35.006% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	0.977	BCRP inhibitor:	0.119
BSEP inhibitor:	0.911

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.15
CYP2C19-inhibitor:	0.57	CYP2C19-substrate:	0.011
CYP2C9-inhibitor:	0.012	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.069
CYP3A4-inhibitor:	0.436	CYP3A4-substrate:	0.004
CYP2B6-substrate:	0.042	CYP2C8-inhibitor:	0.757
HLM stability:	0.961 ? 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):

8.773

Half-life (T1/2):

0.957

ADMET: Toxicity

hERG Blockers:	0.025	hERG Blockers (10um):	0.127
Human Hepatotoxicity (H-HT):	0.488	Drug-induced Liver Injury (DILI):	0.612
AMES Toxicity:	0.204	Rat Oral Acute Toxicity:	0.519
Maximum Recommended Daily Dose:	0.689	Skin Sensitization:	0.597
Carcinogencity:	0.689	Eye Corrosion:	0.001
Eye Irritation:	0.798	Respiratory Toxicity:	0.049
Drug-induced Neurotoxicity:	0.057	Ototoxicity:	0.653
Hematotoxicity:	0.149	Drug-induced Nephrotoxicity:	0.686
Genotoxicity:	0.942	RPMI-8226 Immunitoxicity:	0.056
A549 Cytotoxicity:	0.019	Hek293 Cytotoxicity:	0.035
BCF:	0.605 ? 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:	3.628 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.911 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.233 ? 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
NPO3494	Swietenia mahagoni	Species	Meliaceae	Eukaryota	fruits	n.a.	n.a.	PMID[19902967]
NPO3494	Swietenia mahagoni	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3494	Swietenia mahagoni	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
MIC	1

Activity Type	# Activity
Organism	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
NPT3147	Organism	Kocuria rhizophila	Kocuria rhizophila	MIC	=	12.5	ug.mL-1	PMID[19627125]

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 NPC469503 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	8363
0.1-0.2	39126
0.2-0.3	2099
0.3-0.4	197
0.4-0.5	55
0.5-0.6	9
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
0.6582	Remote Similarity	NPC178932
0.6543	Remote Similarity	NPC292389
0.6506	Remote Similarity	NPC69028
0.6282	Remote Similarity	NPC142113
0.6235	Remote Similarity	NPC165218
0.619	Remote Similarity	NPC469338
0.6047	Remote Similarity	NPC469849
0.6	Remote Similarity	NPC606471
0.5862	Remote Similarity	NPC478178
0.5795	Remote Similarity	NPC478177
0.573	Remote Similarity	NPC236004
0.5714	Remote Similarity	NPC281258
0.5484	Remote Similarity	NPC94763
0.5385	Remote Similarity	NPC276551
0.5269	Remote Similarity	NPC470875
0.5233	Remote Similarity	NPC159927
0.5217	Remote Similarity	NPC329180

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469503 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3306
0.1-0.2	5798
0.2-0.3	46
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