NPASS Compound

Natural Product: NPC253618

Natural Product ID	NPC253618
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	12S,13S-Hydroxyandrographilide
IUPAC Name	(3S,4S)-3-[(1S)-2-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-1-hydroxyethyl]-4-hydroxyoxolan-2-one
Synonyms	12S,13S-Hydroxyandrographilide
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL467963
PubChem CID	24879274
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene 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 58 60 0 0 0 0 0 0 0 0999 V2000 -5.2080 0.3166 1.0903 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8423 0.5448 1.0360 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2025 -0.0271 -0.2070 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9438 0.7166 -1.3469 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4998 -1.4708 -0.4252 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4484 -1.9504 0.5182 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3612 -2.4192 -0.3648 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0132 -1.8774 -0.7001 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7593 -0.6293 0.1388 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7711 0.3423 -0.3688 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5321 1.7709 0.0227 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2597 2.3275 -0.5666 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5045 1.1491 -1.0465 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0807 1.2139 -2.2302 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6079 -0.0810 -0.1950 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4364 0.2017 1.0376 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7998 0.7368 0.7435 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6368 -0.2131 -0.0850 C 0 0 1 0 0 0 0 0 0 0 0 0 4.9864 0.4896 -0.2891 C 0 0 2 0 0 0 0 0 0 0 0 0 5.7311 -0.0929 -1.2832 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6538 0.2255 1.0431 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1227 -0.9993 1.4908 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0635 -1.3983 0.6949 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5513 -2.5442 0.6352 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8561 1.9692 0.1693 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8516 -1.0415 1.5462 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4013 -0.2828 1.8442 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3986 0.2284 1.9838 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7503 1.6747 1.0495 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1477 1.7665 -1.0463 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3389 0.7436 -2.2566 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9168 0.2305 -1.5387 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0441 -1.6590 -1.4029 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6321 -2.8739 0.2834 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5382 -3.2434 -1.1274 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3508 -3.0240 0.5942 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0001 -1.6383 -1.7825 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2686 -2.6564 -0.5194 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5868 0.3298 -1.4942 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4642 1.9160 1.1283 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3600 2.4281 -0.2997 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3001 2.9586 0.1479 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5435 3.0059 -1.3976 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9666 2.1371 -2.8024 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6573 0.3918 -2.6540 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1414 -0.8601 -0.7696 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8534 0.8937 1.6726 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5739 -0.7398 1.6045 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3255 0.8066 1.7391 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2095 -0.4664 -1.0540 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8408 1.5816 -0.4349 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4026 -1.0223 -1.4104 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5009 1.0406 1.7695 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7621 0.1612 0.8484 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4004 2.6336 0.6936 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6252 -0.3176 2.3231 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0993 -1.8780 1.6906 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8056 -1.5264 1.8250 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 1 3 4 1 0 3 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 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 17 25 1 0 9 26 1 1 10 3 1 0 23 18 1 0 15 9 1 0 1 27 1 0 2 28 1 0 2 29 1 0 4 30 1 0 4 31 1 0 4 32 1 0 5 33 1 6 6 34 1 0 7 35 1 0 7 36 1 0 8 37 1 0 8 38 1 0 10 39 1 6 11 40 1 0 11 41 1 0 12 42 1 0 12 43 1 0 14 44 1 0 14 45 1 0 15 46 1 6 16 47 1 0 16 48 1 0 17 49 1 1 18 50 1 6 19 51 1 6 20 52 1 0 21 53 1 0 21 54 1 0 25 55 1 0 26 56 1 0 26 57 1 0 26 58 1 0 M END

Standard InCHIKey	NLYQWYLWLQBMPF-AWAUATEUSA-N
Standard InCHI	InChI=1S/C20H32O6/c1-11-4-5-15-19(2,7-6-16(24)20(15,3)10-21)12(11)8-13(22)17-14(23)9-26-18(17)25/h12-17,21-24H,1,4-10H2,2-3H3/t12-,13+,14-,15+,16-,17+,19+,20+/m1/s1
SMILES	OC[C@]1(C)[C@H](O)CC[C@@]2([C@@H]1CCC(=C)[C@H]2C[C@@H]([C@H]1[C@H](O)COC1=O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	368.22	Volume:	376.275 ? Van der Waals volume.
Dense:	0.979	LogP:	1.502 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.916 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.074 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	18.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.436	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.926	Fsp³:	0.85
MCE-18:	60.919 ? 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:	0.406	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.015 ? 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:	0.308	Promiscuous compounds:	0.487

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.372	MDCK Permeability:	-5.068
Pgp-inhibitor:	0.018	Pgp-substrate:	0.322
PAMPA:	0.986 ? 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):	0.008
20% Bioavailability (F20%):	0.514	30% Bioavailability (F30%):	0.41
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.283	MRP1:	0.578
Plasma Protein Binding (PPB):	56.358%	Volume Distribution (VD):	-0.371
Fu:	44.38% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.618
BSEP inhibitor:	0.517

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.007	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.119	CYP2C9-substrate:	0.005
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.283
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.453
HLM stability:	0.077 ? 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):

9.432

Half-life (T1/2):

1.873

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.189
Human Hepatotoxicity (H-HT):	0.796	Drug-induced Liver Injury (DILI):	0.585
AMES Toxicity:	0.606	Rat Oral Acute Toxicity:	0.358
Maximum Recommended Daily Dose:	0.63	Skin Sensitization:	0.998
Carcinogencity:	0.964	Eye Corrosion:	0.068
Eye Irritation:	0.957	Respiratory Toxicity:	0.681
Drug-induced Neurotoxicity:	0.458	Ototoxicity:	0.617
Hematotoxicity:	0.776	Drug-induced Nephrotoxicity:	0.978
Genotoxicity:	0.819	RPMI-8226 Immunitoxicity:	0.135
A549 Cytotoxicity:	0.746	Hek293 Cytotoxicity:	0.425
BCF:	0.468 ? 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:	3.187 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.807 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.883 ? 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
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1111/ppl.12252]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	leaf	n.a.	PMID[15894448]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	root	n.a.	PMID[15894448]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	aerial parts	purchased in Juhuacun herbal market, Kunming, Yunnan Province, China	2002-Oct	PMID[16562826]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18357994]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21598983]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	leaf	n.a.	PMID[22026410]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8377022]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO3578	Andrographis paniculata	Species	Acanthaceae	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
GI50	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
NPT116	Cell line	HL-60	Homo sapiens	GI50	=	24430.0	nM	DrugMatrix in vitro pharmacology data

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 NPC253618 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	17198
0.1-0.2	26465
0.2-0.3	5808
0.3-0.4	322
0.4-0.5	44
0.5-0.6	11
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	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC77001
0.6724	Remote Similarity	NPC242848
0.6491	Remote Similarity	NPC131813
0.6491	Remote Similarity	NPC139692
0.6441	Remote Similarity	NPC72845
0.6271	Remote Similarity	NPC159763
0.6271	Remote Similarity	NPC278386
0.6271	Remote Similarity	NPC124512
0.6034	Remote Similarity	NPC476602
0.5893	Remote Similarity	NPC476949
0.5645	Remote Similarity	NPC191521
0.5606	Remote Similarity	NPC73911
0.5574	Remote Similarity	NPC152778
0.5574	Remote Similarity	NPC205034
0.5517	Remote Similarity	NPC474433
0.541	Remote Similarity	NPC104560
0.5397	Remote Similarity	NPC234993
0.5397	Remote Similarity	NPC134072
0.5167	Remote Similarity	NPC608380
0.5161	Remote Similarity	NPC478375

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC253618 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6149
0.1-0.2	2864
0.2-0.3	132
0.3-0.4	4
0.4-0.5	0
0.5-0.6	0
0.6-0.7	1
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
0.6271	Remote Similarity	NPD4225	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