NPASS Compound

Natural Product: NPC244335

Natural Product ID	NPC244335
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OVQSVMZESAVYPN-XYPWNMJBSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5316825
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003569] Pregnane steroids [CHEMONTID:0001468] Gluco/mineralocorticoids, progestogins and derivatives

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 56 59 0 0 0 0 0 0 0 0999 V2000 -5.2310 1.2184 0.6611 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1099 0.8864 -0.3453 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9366 0.5244 0.4602 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1413 -0.6727 1.3642 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7442 -1.2595 1.6204 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8866 -0.2731 0.9067 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5464 -0.5457 0.7586 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9532 -1.9160 0.4058 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3054 -2.0378 -0.2544 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1585 -0.8540 -0.0052 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4267 -0.9771 0.3280 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2819 0.2044 0.5781 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5338 0.1178 0.5242 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6471 1.5219 0.9001 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1705 1.2555 1.1068 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6026 0.5203 -0.1216 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1596 1.2490 -1.3225 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1376 0.5774 -0.0593 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4089 0.7144 -1.3565 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0132 1.1948 -1.0187 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6967 0.0769 -0.2932 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0925 -1.0084 -1.2124 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6293 -2.5496 1.2097 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6081 -0.2323 -1.0342 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9683 2.1866 1.1354 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1888 1.3687 0.1187 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2926 0.4648 1.4550 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0142 1.7647 -0.9789 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6019 1.3477 1.1532 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8108 -1.4339 0.9402 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6046 -0.3118 2.2991 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5779 -1.2075 2.7157 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9562 0.6684 1.5526 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9959 -0.3478 1.7962 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2507 -2.5160 -0.1994 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0348 -2.5256 1.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8197 -2.9651 0.0728 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2036 -2.1312 -1.3595 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8431 -1.9766 0.4180 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8621 2.2978 0.1688 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0441 1.7796 1.9263 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6044 2.1773 1.3125 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1183 0.5814 1.9996 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8743 2.3167 -1.2173 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2409 1.1829 -1.4164 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7370 0.8796 -2.2774 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8630 1.5143 0.5246 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3056 -0.1859 -1.9547 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8241 1.5088 -1.9961 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5387 1.4622 -1.9423 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9011 2.0544 -0.3543 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2154 -1.5054 -1.7223 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5902 -0.5005 -2.0992 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8241 -1.7262 -0.8480 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6253 -3.1874 1.9677 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1541 -0.7704 -0.4384 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 6 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 6 5 23 1 0 2 24 1 0 21 3 1 0 21 6 1 0 18 7 1 0 16 10 1 0 1 25 1 0 1 26 1 0 1 27 1 0 2 28 1 6 3 29 1 0 4 30 1 0 4 31 1 0 5 32 1 0 6 33 1 0 7 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 11 39 1 0 14 40 1 0 14 41 1 0 15 42 1 0 15 43 1 0 17 44 1 0 17 45 1 0 17 46 1 0 18 47 1 0 19 48 1 0 19 49 1 0 20 50 1 0 20 51 1 0 22 52 1 0 22 53 1 0 22 54 1 0 23 55 1 0 24 56 1 0 M END

Standard InCHIKey	OVQSVMZESAVYPN-XYPWNMJBSA-N
Standard InCHI	InChI=1S/C21H32O3/c1-12(22)17-11-18(24)19-15-5-4-13-10-14(23)6-8-20(13,2)16(15)7-9-21(17,19)3/h10,12,15-19,22,24H,4-9,11H2,1-3H3/t12-,15?,16?,17?,18?,19?,20-,21+/m0/s1
SMILES	C[C@@H](C1CC(C2C3CCC4=CC(=O)CC[C@]4(C)C3CC[C@]12C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	332.24	Volume:	358.644 ? Van der Waals volume.
Dense:	0.926	LogP:	2.192 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.514 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.005 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	21.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.773	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.427	Fsp³:	0.857
MCE-18:	70.667 ? 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:	0.409	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.034 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.007 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.315	Promiscuous compounds:	0.185

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.767	MDCK Permeability:	-4.966
Pgp-inhibitor:	0.019	Pgp-substrate:	0.255
PAMPA:	0.889 ? 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):	0.004
20% Bioavailability (F20%):	0.442	30% Bioavailability (F30%):	0.196
50% Bioavailability (F50%):	0.924

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.781	MRP1:	0.974
Plasma Protein Binding (PPB):	79.936%	Volume Distribution (VD):	-0.428
Fu:	17.262% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.521
OATP1B3 inhibitor:	0.761	BCRP inhibitor:	0.059
BSEP inhibitor:	0.842

ADMET: Metabolism

CYP1A2-inhibitor:	0.036	CYP1A2-substrate:	0.024
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.708	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.004	CYP2D6-substrate:	0.004
CYP3A4-inhibitor:	0.989	CYP3A4-substrate:	0.401
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.881
HLM stability:	0.958 ? 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):

15.956

Half-life (T1/2):

1.851

ADMET: Toxicity

hERG Blockers:	0.122	hERG Blockers (10um):	0.659
Human Hepatotoxicity (H-HT):	0.785	Drug-induced Liver Injury (DILI):	0.278
AMES Toxicity:	0.252	Rat Oral Acute Toxicity:	0.409
Maximum Recommended Daily Dose:	0.872	Skin Sensitization:	0.624
Carcinogencity:	0.915	Eye Corrosion:	0.01
Eye Irritation:	0.4	Respiratory Toxicity:	0.694
Drug-induced Neurotoxicity:	0.701	Ototoxicity:	0.561
Hematotoxicity:	0.073	Drug-induced Nephrotoxicity:	0.205
Genotoxicity:	0.387	RPMI-8226 Immunitoxicity:	0.062
A549 Cytotoxicity:	0.381	Hek293 Cytotoxicity:	0.695
BCF:	0.653 ? 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:	3.48 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.165 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.29 ? 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
NPO14263	Cipadessa baccifera	Species	Meliaceae	Eukaryota	leaves	n.a.	n.a.	PMID[20666364]
NPO14263	Cipadessa baccifera	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32468815]
NPO14263	Cipadessa baccifera	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14263	Cipadessa baccifera	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14263	Cipadessa baccifera	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14263	Cipadessa baccifera	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14263	Cipadessa baccifera	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

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 NPC244335 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	17676
0.1-0.2	27749
0.2-0.3	4241
0.3-0.4	133
0.4-0.5	25
0.5-0.6	24
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
0.7255	Intermediate Similarity	NPC214043
0.7255	Intermediate Similarity	NPC85774
0.6182	Remote Similarity	NPC327115
0.6071	Remote Similarity	NPC237712
0.6038	Remote Similarity	NPC307176
0.6038	Remote Similarity	NPC321874
0.6	Remote Similarity	NPC227064
0.6	Remote Similarity	NPC329043
0.6	Remote Similarity	NPC58841
0.6	Remote Similarity	NPC161423
0.5789	Remote Similarity	NPC328539
0.5714	Remote Similarity	NPC282593
0.5614	Remote Similarity	NPC257176
0.5614	Remote Similarity	NPC35734
0.5614	Remote Similarity	NPC144258
0.5614	Remote Similarity	NPC159577
0.5614	Remote Similarity	NPC115023
0.5614	Remote Similarity	NPC602429
0.5593	Remote Similarity	NPC119416
0.5556	Remote Similarity	NPC139397
0.5517	Remote Similarity	NPC149203
0.55	Remote Similarity	NPC185936
0.55	Remote Similarity	NPC168027
0.5424	Remote Similarity	NPC249312
0.5357	Remote Similarity	NPC2634
0.5357	Remote Similarity	NPC265782
0.5357	Remote Similarity	NPC251929
0.5333	Remote Similarity	NPC310010
0.5333	Remote Similarity	NPC326627
0.5231	Remote Similarity	NPC111015
0.5079	Remote Similarity	NPC309603
0.5079	Remote Similarity	NPC192428
0.5079	Remote Similarity	NPC18509
0.5079	Remote Similarity	NPC319582

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC244335 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6633
0.1-0.2	2217
0.2-0.3	207
0.3-0.4	53
0.4-0.5	28
0.5-0.6	10
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	Drug ID	Developmental Stage
0.6038	Remote Similarity	NPD4747	Phase 4
0.6	Remote Similarity	NPD3666	Phase 4
0.5714	Remote Similarity	NPD4221	Phase 4
0.5614	Remote Similarity	NPD3618	Phase 1
0.5424	Remote Similarity	NPD4693	Phase 3
0.5357	Remote Similarity	NPD4691	Approved
0.5333	Remote Similarity	NPD4753	Phase 2
0.5246	Remote Similarity	NPD5737	Phase 4
0.5079	Remote Similarity	NPD4697	Phase 2
0.5079	Remote Similarity	NPD4754	Approved
0.5079	Remote Similarity	NPD4755	Phase 4
0.5079	Remote Similarity	NPD6672	Phase 4

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