NPASS Compound

Natural Product: NPC473310

Natural Product ID	NPC473310
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Manzamine E
IUPAC Name	n.a.
Synonyms	Manzamine E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL399493
PubChem CID	44445401
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001140] Harmala alkaloids

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 86 93 0 0 0 0 0 0 0 0999 V2000 -2.6449 3.3308 1.4493 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3603 2.2089 2.0312 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1558 1.8261 2.7397 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2515 0.8500 2.1460 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5840 -0.3835 1.4847 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7047 -0.7571 0.7026 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1346 0.0464 -0.2436 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0925 0.8546 -0.9237 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4626 1.4034 -2.2542 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6801 2.3439 -2.6906 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6601 2.4215 -1.6694 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.5388 3.5223 -1.6342 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9162 4.8091 -1.1477 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1421 4.7728 0.0826 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7437 4.4572 1.4099 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2664 1.1304 -1.4181 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2069 0.1421 -0.9001 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1546 -0.9925 -1.8712 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2182 -2.2735 -1.0157 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8586 -3.2999 -1.9183 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6927 -4.7125 -1.3502 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6800 -4.9580 -0.2920 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2565 -5.7438 0.5379 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0484 -4.4380 -0.0647 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0597 -3.0167 0.4582 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6699 -2.5884 0.9466 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9381 -1.8374 0.0587 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6336 -0.4518 0.4068 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5414 0.1448 -0.5376 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5226 -0.3053 0.3069 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8704 -0.2795 -0.0814 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2029 0.2077 -1.3293 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2061 0.6545 -2.1552 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9563 0.6024 -1.7289 N 0 0 0 0 0 0 0 0 0 0 0 0 5.6657 -0.7475 0.9207 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0227 -0.9290 1.0507 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5881 -1.4355 2.2091 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7337 -1.7557 3.2405 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3553 -1.5705 3.1062 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8084 -1.0672 1.9515 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5449 -0.7954 1.5651 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.6968 -1.4274 2.3898 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6366 3.4528 1.0075 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1887 1.4699 2.0130 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4825 1.4349 3.7628 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5864 2.7354 3.0101 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6374 1.4151 1.7090 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3424 0.4780 3.0960 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2067 -1.6776 0.9005 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1111 1.8223 -0.3492 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7870 0.7266 -3.0229 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3126 2.1338 -2.0656 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3335 3.3369 -2.9662 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1222 1.9021 -3.6328 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4503 3.3074 -1.0931 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9472 3.7255 -2.7103 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6760 5.6465 -1.1899 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2100 5.1053 -1.9930 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6366 5.8078 0.2548 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2212 4.1445 -0.1142 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0076 4.5088 2.2381 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3970 5.3733 1.6381 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9982 1.2573 -0.6022 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7674 0.7404 -2.3313 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0050 -0.9784 -2.5948 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2402 -1.0685 -2.4504 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1948 -2.6220 -0.8028 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2840 -3.3105 -2.8711 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8949 -3.0702 -2.1749 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6427 -4.8078 -1.0057 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8188 -5.4015 -2.2107 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6178 -4.4451 -1.0247 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5710 -5.1449 0.6318 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8082 -3.0039 1.2836 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4429 -2.3009 -0.2980 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1719 -3.5322 1.2844 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9058 -1.9590 1.8585 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6181 -0.0908 0.6524 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2314 0.2545 -1.6932 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3926 1.0516 -3.1482 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7157 -0.6811 0.2446 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6422 -1.5954 2.3589 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1196 -2.1578 4.1760 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6980 -1.8291 3.9313 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7424 -0.9321 2.1843 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1947 -1.1849 3.2202 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 2 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 1 0 14 15 1 0 11 16 1 0 16 17 1 0 17 18 1 6 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 7 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 31 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 38 39 1 0 39 40 2 0 40 41 1 0 5 42 1 1 15 1 1 0 28 17 1 0 34 29 1 0 40 35 1 0 28 5 1 0 41 30 1 0 17 8 1 0 27 19 1 0 1 43 1 0 2 44 1 0 3 45 1 0 3 46 1 0 4 47 1 0 4 48 1 0 6 49 1 0 8 50 1 0 9 51 1 0 9 52 1 0 10 53 1 0 10 54 1 0 12 55 1 0 12 56 1 0 13 57 1 0 13 58 1 0 14 59 1 0 14 60 1 0 15 61 1 0 15 62 1 0 16 63 1 0 16 64 1 0 18 65 1 0 18 66 1 0 19 67 1 1 20 68 1 0 20 69 1 0 21 70 1 0 21 71 1 0 24 72 1 0 24 73 1 0 25 74 1 0 25 75 1 0 26 76 1 0 26 77 1 0 28 78 1 1 32 79 1 0 33 80 1 0 36 81 1 0 37 82 1 0 38 83 1 0 39 84 1 0 41 85 1 0 42 86 1 0 M END

Standard InCHIKey	LTHULOBARTYAMF-ASQXKTFQSA-N
Standard InCHI	InChI=1S/C36H44N4O2/c41-26-10-9-20-40-25(13-14-26)22-35-24-39-19-8-4-2-1-3-7-17-36(42,34(35)40)23-29(30(35)16-21-39)32-33-28(15-18-37-32)27-11-5-6-12-31(27)38-33/h1,3,5-6,11-12,15,18,23,25,30,34,38,42H,2,4,7-10,13-14,16-17,19-22,24H2/b3-1-/t25-,30?,34+,35-,36-/m0/s1
SMILES	C1=CCC[C@@]2(C=C(C3CCN(CCCC1)C[C@]13C[C@@H]3CCC(=O)CCCN3[C@@H]21)c1c2c(ccn1)c1ccccc1[nH]2)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	564.35	Volume:	600.6 ? Van der Waals volume.
Dense:	0.94	LogP:	3.83 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.31 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.656 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	47.0
TPSA:	72.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	8.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.342	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.506	Fsp³:	0.556
MCE-18:	198.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.164	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.815 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.754 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.532

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.318	MDCK Permeability:	-5.08
Pgp-inhibitor:	0.004	Pgp-substrate:	0.004
PAMPA:	0.004 ? 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%):	0.0	30% Bioavailability (F30%):	0.005
50% Bioavailability (F50%):	0.059

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.986	MRP1:	0.987
Plasma Protein Binding (PPB):	85.16%	Volume Distribution (VD):	0.42
Fu:	15.234% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.363
OATP1B3 inhibitor:	0.977	BCRP inhibitor:	0.137
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.403	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.581
CYP2D6-inhibitor:	0.803	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.922 ? 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):

7.408

Half-life (T1/2):

0.61

ADMET: Toxicity

hERG Blockers:	0.746	hERG Blockers (10um):	0.385
Human Hepatotoxicity (H-HT):	0.577	Drug-induced Liver Injury (DILI):	0.256
AMES Toxicity:	0.185	Rat Oral Acute Toxicity:	0.903
Maximum Recommended Daily Dose:	0.986	Skin Sensitization:	0.993
Carcinogencity:	0.47	Eye Corrosion:	0.0
Eye Irritation:	0.031	Respiratory Toxicity:	0.972
Drug-induced Neurotoxicity:	0.893	Ototoxicity:	0.726
Hematotoxicity:	0.134	Drug-induced Nephrotoxicity:	0.969
Genotoxicity:	0.823	RPMI-8226 Immunitoxicity:	0.262
A549 Cytotoxicity:	0.936	Hek293 Cytotoxicity:	0.934
BCF:	0.574 ? 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:	3.312 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.747 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.214 ? 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
NPO32531	sponge sp.	Species	n.a.	n.a.	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape, Manado Bay, Indonesia	2011-MAR	PMID[12828469]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15332848]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	n.a.	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	2004-Mar	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	Indonesian	n.a.	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	2002-May	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[28452477]
NPO33515	xestospongia ashmorica	Species	Petrosiidae	Eukaryota	n.a.	Philippine	n.a.	PMID[8946747]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO32531	sponge sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]

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
Inhibition	3
IC50	14
EC50	2
ED50	1
MIC	3
IC90	3

Activity Type	# Activity
Individual protein	3
Cell line	1
Organism	22

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	Inhibition	=	53.6	%	PMID[23398362]
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	IC50	=	25000.0	nM	PMID[22413887]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1864	Cell line	L5178Y	Mus musculus	ED50	=	6.6	ug ml-1	PMID[8482949]
NPT86	Organism	Mycobacterium intracellulare	Mycobacterium intracellulare	IC50	=	12.5	ug.mL-1	PMID[15332845]
NPT776	Organism	Spodoptera littoralis	Spodoptera littoralis	Inhibition	=	0.0	%	PMID[20061160]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	3.4	ug.mL-1	PMID[23434420]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	4.76	ug.mL-1	PMID[15974580]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	3.76	ug.mL-1	PMID[18977148]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	3.8	ug.mL-1	PMID[24177359]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC90	=	6.8	ug.mL-1	PMID[18625769]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	3.8	ug.mL-1	PMID[22652254]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	13100.0	nM	PMID[16933872]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	IC50	=	13.1	ug.mL-1	PMID[8864235]

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 NPC473310 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	31516
0.1-0.2	17804
0.2-0.3	463
0.3-0.4	39
0.4-0.5	7
0.5-0.6	9
0.6-0.7	13
0.7-0.8	0
0.8-0.85	3
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.85	High Similarity	NPC41679
0.8265	Intermediate Similarity	NPC189202
0.8235	Intermediate Similarity	NPC473312
0.8235	Intermediate Similarity	NPC160752
0.7938	Intermediate Similarity	NPC166492
0.7857	Intermediate Similarity	NPC473362
0.7549	Intermediate Similarity	NPC479685
0.6729	Remote Similarity	NPC607194
0.6698	Remote Similarity	NPC487892
0.6698	Remote Similarity	NPC6215
0.6696	Remote Similarity	NPC479688
0.6549	Remote Similarity	NPC471506
0.6481	Remote Similarity	NPC476451
0.6481	Remote Similarity	NPC253069
0.6481	Remote Similarity	NPC607417
0.646	Remote Similarity	NPC475258
0.6435	Remote Similarity	NPC476492
0.6228	Remote Similarity	NPC909
0.6228	Remote Similarity	NPC475338
0.6066	Remote Similarity	NPC476493
0.5877	Remote Similarity	NPC265576
0.5856	Remote Similarity	NPC473757
0.5833	Remote Similarity	NPC476491
0.5726	Remote Similarity	NPC479681
0.5564	Remote Similarity	NPC471564
0.5492	Remote Similarity	NPC81175
0.5254	Remote Similarity	NPC250835
0.5254	Remote Similarity	NPC604135
0.5242	Remote Similarity	NPC602860

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473310 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5067
0.1-0.2	4009
0.2-0.3	74
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