NPASS Compound

Natural Product: NPC100734

Natural Product ID	NPC100734
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methyl (1S,15R,17S,18S,19R,20R)-6,18-Dimethoxy-17-(3,4,5-Trimethoxybenzoyl)Oxy-1,3,11,12,14,15,16,17,18,19,20,21-Dodecahydroyohimban-19-Carboxylate
IUPAC Name	methyl (1S,15R,17S,18S,19R,20R)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyl)oxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1396912
PubChem CID	6604180
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001786] Yohimbine 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 84 89 0 0 0 0 0 0 0 0999 V2000 -11.2831 -1.5636 0.0843 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0259 -1.8390 -0.4741 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.8845 -1.1060 -0.1751 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0106 -0.0601 0.7154 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8844 0.6946 1.0364 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6874 0.3700 0.4539 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4452 0.9511 0.6018 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9048 2.0828 1.3861 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4805 1.9322 1.7951 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7904 0.8340 1.1995 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.3842 0.9601 1.4112 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5464 -0.0393 0.6845 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9119 0.2842 0.9229 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6876 -0.1678 -0.2990 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3042 0.7852 -1.4020 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1395 0.5336 -1.7508 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8866 -0.2786 -0.7394 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3615 -0.2838 -0.9432 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1552 0.7172 -0.1933 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5746 0.2519 -0.2015 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2428 -0.7306 -0.8302 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.5411 -0.6725 -0.4393 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6672 -1.4086 -0.7449 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7792 1.7931 -2.1485 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3462 1.9876 -3.2749 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7903 2.8613 -1.2801 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3733 4.1154 -1.5566 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1406 0.6732 -2.5075 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8615 1.8490 -2.7198 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0759 -0.1492 -0.0768 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7710 -1.3454 -0.1017 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1376 -2.4338 -0.3236 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1946 -1.4469 0.1111 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8524 -2.6561 0.0878 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2129 -2.7379 0.2898 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9883 -1.6238 0.5251 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3272 -0.3961 0.5497 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9642 -0.3193 0.3468 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1240 0.7220 0.7885 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5325 2.0119 0.8324 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3586 -1.7319 0.7260 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8284 -1.9123 2.0581 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8895 -3.9720 0.2669 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1031 -5.1415 0.0247 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2092 -1.5798 1.2061 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.6950 -0.5839 -0.2165 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.9786 -2.4106 -0.1690 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9617 0.1858 1.1677 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9310 1.5163 1.7229 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0354 3.0600 0.8378 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5873 2.1889 2.2782 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4614 1.7834 2.9141 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9323 2.9022 1.6352 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0555 2.0132 1.3001 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2255 0.7537 2.5153 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7088 -1.0168 1.2362 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0775 1.3626 1.1261 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3374 -0.2586 1.7945 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3776 -1.2144 -0.4767 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4504 1.8180 -0.9824 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0901 -0.0747 -2.7122 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5654 -1.3557 -0.9480 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6300 -0.1972 -2.0183 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7470 -1.2978 -0.6214 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1926 1.7323 -0.6399 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8532 -1.4344 -1.5111 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5800 -2.2345 -1.4447 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3014 4.3432 -2.6382 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7903 4.8751 -0.9727 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4186 4.1759 -1.1701 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5101 1.7431 -3.5890 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1946 2.7264 -2.9059 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4587 2.1234 -1.8184 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3193 -3.5960 -0.0917 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4970 0.6776 0.3776 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0352 2.2724 -0.1381 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8025 2.0262 1.6653 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3267 2.7681 0.9722 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0579 -1.6722 2.8131 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0994 -2.9872 2.2215 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6950 -1.2385 2.2704 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7154 -6.0484 0.1741 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2655 -5.1934 0.7592 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6486 -5.0478 -0.9667 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 4 5 1 0 5 6 2 0 6 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 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 16 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 15 28 1 0 28 29 1 0 14 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 37 39 1 0 39 40 1 0 36 41 1 0 41 42 1 0 35 43 1 0 43 44 1 0 23 3 1 0 38 33 1 0 22 6 1 0 20 7 2 0 19 10 1 0 17 12 1 0 1 45 1 0 1 46 1 0 1 47 1 0 4 48 1 0 5 49 1 0 8 50 1 0 8 51 1 0 9 52 1 0 9 53 1 0 11 54 1 0 11 55 1 0 12 56 1 1 13 57 1 0 13 58 1 0 14 59 1 6 15 60 1 1 16 61 1 6 17 62 1 6 18 63 1 0 18 64 1 0 19 65 1 6 21 66 1 0 23 67 1 0 27 68 1 0 27 69 1 0 27 70 1 0 29 71 1 0 29 72 1 0 29 73 1 0 34 74 1 0 38 75 1 0 40 76 1 0 40 77 1 0 40 78 1 0 42 79 1 0 42 80 1 0 42 81 1 0 44 82 1 0 44 83 1 0 44 84 1 0 M END

Standard InCHIKey	QEVHRUUCFGRFIF-KWTXYEQSSA-N
Standard InCHI	InChI=1S/C33H40N2O9/c1-38-19-7-8-20-21-9-10-35-16-18-13-27(44-32(36)17-11-25(39-2)30(41-4)26(12-17)40-3)31(42-5)28(33(37)43-6)22(18)15-24(35)29(21)34-23(20)14-19/h7-8,11-12,14,18,22,24,27-28,31,34H,9-10,13,15-16H2,1-6H3/t18-,22+,24-,27-,28+,31+/m0/s1
SMILES	COc1ccc2c3CCN4C[C@@H]5C[C@@H]([C@H]([C@@H]([C@@H]5C[C@H]4c3[nH]c2c1)C(=O)OC)OC)OC(=O)c1cc(c(c(c1)OC)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	608.27	Volume:	605.363 ? Van der Waals volume.
Dense:	1.005	LogP:	2.704 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.748 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.569 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	33.0
TPSA:	117.78 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.374	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.342	Fsp³:	0.515
MCE-18:	123.84 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.205	Fluc inhibitor:	0.321 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.391 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.306 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.98

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.139	MDCK Permeability:	-4.856
Pgp-inhibitor:	0.02	Pgp-substrate:	0.507
PAMPA:	0.002 ? 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%):	0.028	30% Bioavailability (F30%):	0.009
50% Bioavailability (F50%):	0.959

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.902	MRP1:	0.999
Plasma Protein Binding (PPB):	97.413%	Volume Distribution (VD):	0.082
Fu:	2.066% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.841
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.052
CYP2C19-inhibitor:	0.993	CYP2C19-substrate:	0.013
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.098
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.007 ? 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):

7.305

Half-life (T1/2):

0.916

ADMET: Toxicity

hERG Blockers:	0.688	hERG Blockers (10um):	0.661
Human Hepatotoxicity (H-HT):	0.318	Drug-induced Liver Injury (DILI):	0.805
AMES Toxicity:	0.57	Rat Oral Acute Toxicity:	0.621
Maximum Recommended Daily Dose:	0.907	Skin Sensitization:	0.729
Carcinogencity:	0.892	Eye Corrosion:	0.0
Eye Irritation:	0.028	Respiratory Toxicity:	0.934
Drug-induced Neurotoxicity:	0.907	Ototoxicity:	0.762
Hematotoxicity:	0.203	Drug-induced Nephrotoxicity:	0.952
Genotoxicity:	0.782	RPMI-8226 Immunitoxicity:	0.293
A549 Cytotoxicity:	0.604	Hek293 Cytotoxicity:	0.765
BCF:	0.826 ? 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:	3.848 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.163 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.656 ? 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
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s11240-015-0798-z]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.fitote.2006.01.011]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.plaphy.2005.07.013]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1078/0176-1617-00195]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1155/2014/609649]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10757735]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14735439]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	callus	n.a.	PMID[15715262]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18220354]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28445039]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	Roots	n.a.	n.a.	PMID[30024167]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32560389]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36336219]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38217369]
NPO7282	Rauvolfia serpentina	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7282	Rauvolfia serpentina	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7282	Rauvolfia serpentina	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7282	Rauvolfia serpentina	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4391	Hypericum perforatum	Species	Hypericaceae	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
Potency	15
AC50	2

Activity Type	# Activity
Individual protein	16
Protein-protein interaction	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT210	Individual protein	Thyroid stimulating hormone receptor	Homo sapiens	Potency	=	15848.9	nM	PubChem BioAssay data set
NPT211	Individual protein	Hypoxia-inducible factor 1 alpha	Homo sapiens	Potency	=	10000.0	nM	PubChem BioAssay data set
NPT2930	Individual protein	Hemoglobin beta chain	Homo sapiens	Potency	=	15848.9	nM	PubChem BioAssay data set
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	Potency	=	7943.3	nM	PubChem BioAssay data set
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	AC50	=	7943.28	nM	PubChem BioAssay data set
NPT208	Individual protein	Cytochrome P450 1A2	Homo sapiens	AC50	=	15848.93	nM	PubChem BioAssay data set
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	=	17782.8	nM	PubChem BioAssay data set
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	12589.3	nM	PubChem BioAssay data set
NPT48	Individual protein	Lysine-specific demethylase 4D-like	Homo sapiens	Potency	=	10000.0	nM	PubChem BioAssay data set
NPT94	Individual protein	Aldehyde dehydrogenase 1A1	Homo sapiens	Potency	=	6309.6	nM	PubChem BioAssay data set
NPT444	Individual protein	Ubiquitin carboxyl-terminal hydrolase 1	Homo sapiens	Potency	n.a.	31622.8	nM	PubChem BioAssay data set
NPT93	Individual protein	Survival motor neuron protein	Homo sapiens	Potency	=	1412.5	nM	PubChem BioAssay data set
NPT197	Protein-protein interaction	Menin/Histone-lysine N-methyltransferase MLL	Homo sapiens	Potency	=	14125.4	nM	PubChem BioAssay data set
NPT45	Individual protein	Ubiquitin carboxyl-terminal hydrolase 2	Homo sapiens	Potency	=	10000.0	nM	PubChem BioAssay data set
NPT5	Individual protein	Histone-lysine N-methyltransferase, H3 lysine-9 specific 3	Homo sapiens	Potency	n.a.	8912.5	nM	PubChem BioAssay data set

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 NPC100734 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	26953
0.1-0.2	22409
0.2-0.3	411
0.3-0.4	54
0.4-0.5	26
0.5-0.6	1
0.6-0.7	0
0.7-0.8	2
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC88923
1.0	High Similarity	NPC315634
0.8444	Intermediate Similarity	NPC191489
0.7708	Intermediate Similarity	NPC284685
0.55	Remote Similarity	NPC21638

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC100734 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4746
0.1-0.2	4326
0.2-0.3	69
0.3-0.4	1
0.4-0.5	4
0.5-0.6	0
0.6-0.7	0
0.7-0.8	2
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD7803	Phase 4
0.8444	Intermediate Similarity	NPD7708	Phase 4
0.7708	Intermediate Similarity	NPD7955	Phase 4
0.7708	Intermediate Similarity	NPD7956	Approved

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