NPASS Compound

Natural Product: NPC470224

Natural Product ID	NPC470224
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-Hydroxy-24,25,26,27-Tetranortirucall-7-Ene-23(21)-Lactone
IUPAC Name	4-[(3R,5R,9R,10R,13S,14S,17S)-3-hydroxy-4,4,10,13,14-pentamethyl-2,3,5,6,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]oxolan-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1835431
PubChem CID	12992565
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones

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 69 73 0 0 0 0 0 0 0 0999 V2000 8.0573 -0.0230 -1.1690 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8215 0.1901 -1.0781 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0991 1.0856 -1.8542 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7503 1.1375 -1.3945 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5518 -0.2535 -0.8515 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8959 -0.4664 -0.1320 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5033 -0.3509 0.1910 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4133 -1.8042 0.6355 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9161 -2.1470 0.6129 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3135 -0.7888 0.8168 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1128 0.0246 -0.2125 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7460 -0.4229 -1.5924 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7677 1.4583 -0.0176 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3285 1.7600 0.2424 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5886 0.6240 -0.0726 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1085 -0.6710 0.5115 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9154 -1.6869 0.7572 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3633 -1.6913 0.4949 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7568 -0.4008 -0.1435 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0021 0.7964 0.4332 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0812 0.7762 1.9397 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6261 2.0744 -0.0430 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3023 1.8374 -1.3762 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5311 1.0060 -1.1059 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2381 -0.1770 -0.2183 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7973 -1.4054 -0.9569 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9305 -0.1116 1.0961 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0622 0.6423 -2.3400 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6266 -0.3518 2.2245 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7219 1.8435 -0.5622 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0648 1.3815 -2.2320 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5312 -1.0350 -1.6298 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0746 -1.5606 -0.0344 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8777 0.0434 0.8696 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8306 0.3065 1.0486 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7028 -1.8443 1.7145 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9983 -2.4731 0.0028 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6606 -2.8606 1.4186 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7149 -2.5927 -0.3741 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9241 -1.1670 -1.5851 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4847 0.4842 -2.2135 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5732 -0.9050 -2.1520 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1412 1.9989 -0.9402 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4387 1.8587 0.7904 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2458 2.1327 1.2841 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0483 2.6169 -0.4073 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6749 0.5581 -1.1778 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5044 -2.6173 1.1919 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9705 -1.9526 1.3830 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5561 -2.5222 -0.2433 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4125 -0.4680 -1.2207 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2426 1.3227 2.4174 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0031 1.3207 2.2543 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0837 -0.2352 2.3702 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9471 2.9147 -0.1628 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4330 2.4265 0.6575 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6420 1.3530 -2.1101 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6363 2.7953 -1.8330 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2902 1.6857 -0.6364 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7706 -2.2693 -0.2920 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7820 -1.1882 -1.3920 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0900 -1.5823 -1.7941 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2068 0.9444 1.3879 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9360 -0.6260 1.0283 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4146 -0.5918 1.9307 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0365 0.6002 -2.3482 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0901 -1.1758 2.8032 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2536 0.5306 2.3155 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6554 -0.1111 2.7242 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 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 6 11 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 1 20 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 10 29 1 1 6 2 1 0 11 7 1 0 20 15 1 0 16 10 1 0 25 19 1 0 4 30 1 0 4 31 1 0 5 32 1 0 6 33 1 0 6 34 1 0 7 35 1 1 8 36 1 0 8 37 1 0 9 38 1 0 9 39 1 0 12 40 1 0 12 41 1 0 12 42 1 0 13 43 1 0 13 44 1 0 14 45 1 0 14 46 1 0 15 47 1 6 17 48 1 0 18 49 1 0 18 50 1 0 19 51 1 6 21 52 1 0 21 53 1 0 21 54 1 0 22 55 1 0 22 56 1 0 23 57 1 0 23 58 1 0 24 59 1 1 26 60 1 0 26 61 1 0 26 62 1 0 27 63 1 0 27 64 1 0 27 65 1 0 28 66 1 0 29 67 1 0 29 68 1 0 29 69 1 0 M END

Standard InCHIKey	JUXMUKOXQMUUKD-GUWAIDGQSA-N
Standard InCHI	InChI=1S/C26H40O3/c1-23(2)20-7-6-19-18(24(20,3)11-10-21(23)27)9-13-25(4)17(8-12-26(19,25)5)16-14-22(28)29-15-16/h6,16-18,20-21,27H,7-15H2,1-5H3/t16?,17-,18-,20-,21+,24+,25-,26+/m0/s1
SMILES	O=C1OCC(C1)[C@@H]1CC[C@]2([C@@]1(C)CC[C@H]1C2=CC[C@@H]2[C@]1(C)CC[C@H](C2(C)C)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	400.3	Volume:	436.568 ? Van der Waals volume.
Dense:	0.917	LogP:	3.971 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.615 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.974 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	26.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.466	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.669	Fsp³:	0.885
MCE-18:	92.98 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.757	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? 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:	0.432	Promiscuous compounds:	0.25

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.768	MDCK Permeability:	-4.608
Pgp-inhibitor:	0.166	Pgp-substrate:	0.318
PAMPA:	0.814 ? 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):	0.0
20% Bioavailability (F20%):	0.292	30% Bioavailability (F30%):	0.057
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.953	MRP1:	0.875
Plasma Protein Binding (PPB):	89.022%	Volume Distribution (VD):	-0.087
Fu:	13.606% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.783
BSEP inhibitor:	0.607

ADMET: Metabolism

CYP1A2-inhibitor:	0.91	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.056
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.091
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.992
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.993
HLM stability:	0.32 ? 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):

10.937

Half-life (T1/2):

0.529

ADMET: Toxicity

hERG Blockers:	0.088	hERG Blockers (10um):	0.368
Human Hepatotoxicity (H-HT):	0.772	Drug-induced Liver Injury (DILI):	0.684
AMES Toxicity:	0.641	Rat Oral Acute Toxicity:	0.612
Maximum Recommended Daily Dose:	0.869	Skin Sensitization:	0.99
Carcinogencity:	0.953	Eye Corrosion:	0.018
Eye Irritation:	0.525	Respiratory Toxicity:	0.744
Drug-induced Neurotoxicity:	0.555	Ototoxicity:	0.549
Hematotoxicity:	0.749	Drug-induced Nephrotoxicity:	0.911
Genotoxicity:	0.919	RPMI-8226 Immunitoxicity:	0.132
A549 Cytotoxicity:	0.721	Hek293 Cytotoxicity:	0.598
BCF:	2.008 ? 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:	4.309 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.652 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.198 ? 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
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	twigs and leaves	Yunnan Province, China	2008-OCT	PMID[21954912]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21954912]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	twig	n.a.	PMID[21954912]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11885	Dysoxylum lenticellatum	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
Activity	1

Activity Type	# Activity
Tissue	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
NPT177	Tissue	Aorta	Rattus norvegicus	Activity	=	37.5	%	PMID[22694318]

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 NPC470224 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	18727
0.1-0.2	24396
0.2-0.3	5790
0.3-0.4	746
0.4-0.5	156
0.5-0.6	20
0.6-0.7	18
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	NPC210268
0.7143	Intermediate Similarity	NPC190604
0.6885	Remote Similarity	NPC470223
0.6452	Remote Similarity	NPC30166
0.6418	Remote Similarity	NPC471293
0.6406	Remote Similarity	NPC470077
0.6406	Remote Similarity	NPC125399
0.6406	Remote Similarity	NPC486522
0.6406	Remote Similarity	NPC470049
0.6324	Remote Similarity	NPC484791
0.6324	Remote Similarity	NPC484790
0.6308	Remote Similarity	NPC486523
0.6269	Remote Similarity	NPC472240
0.6269	Remote Similarity	NPC262858
0.6094	Remote Similarity	NPC328052
0.6029	Remote Similarity	NPC484789
0.6029	Remote Similarity	NPC484801
0.6029	Remote Similarity	NPC484786
0.6029	Remote Similarity	NPC484787
0.6029	Remote Similarity	NPC484788
0.5942	Remote Similarity	NPC324598
0.5857	Remote Similarity	NPC5358
0.5857	Remote Similarity	NPC216260
0.5538	Remote Similarity	NPC1319
0.5429	Remote Similarity	NPC142361
0.5429	Remote Similarity	NPC474684
0.5352	Remote Similarity	NPC470375
0.5352	Remote Similarity	NPC470376
0.5342	Remote Similarity	NPC273669
0.5342	Remote Similarity	NPC484802
0.5342	Remote Similarity	NPC118647
0.5286	Remote Similarity	NPC318390
0.5256	Remote Similarity	NPC609156
0.5224	Remote Similarity	NPC235341
0.5217	Remote Similarity	NPC196485
0.5217	Remote Similarity	NPC245972
0.5211	Remote Similarity	NPC472227
0.5211	Remote Similarity	NPC472228
0.5139	Remote Similarity	NPC470050
0.5139	Remote Similarity	NPC470051

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470224 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6653
0.1-0.2	2356
0.2-0.3	137
0.3-0.4	3
0.4-0.5	1
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